Originally published 20 March 2020; corrected 22 October 2021

science.sciencemag.org/content/367/6484/eaay6690/suppl/DC1

Supplementary Materials for

The genetic architecture of the human cerebral cortex
Katrina L. Grasby*†, Neda Jahanshad*†, Jodie N. Painter‡, Lucía Colodro-Conde‡, Janita Bralten‡,
Derrek P. Hibar‡, Penelope A. Lind‡, Fabrizio Pizzagalli‡, Christopher R. K. Ching, Mary Agnes B.
McMahon, Natalia Shatokhina, Leo C. P. Zsembik, Sophia I. Thomopoulos, Alyssa H. Zhu, L achlan T.
Strike, Ingrid Agartz, Saud Alhusaini, Marcio A. A. Almeida, Dag Alnæs, Inge K. Amlien, Micael
Andersson, Tyler Ard, Nicola J. Armstrong, Allison Ashley-Koch, Joshua R. Atkins, Manon Bernard,
Rachel M. Brouwer, Elizabeth E. L. Buimer, Robin Bülow, Christian Bürger, Dara M. Cannon, Mallar
Chakravarty, Qiang Chen, Joshua W. Cheung, Baptiste Couvy-Duchesne, Anders M. Dale, Shareefa
Dalvie, Tânia K. de Araujo, Greig I. de Zubicaray, Sonja M. C. de Zwarte, Anouk den Braber, Nhat
Trung Doan, Katharina Dohm, Stefan Ehrlich, Hannah-Ruth Engelbrecht, Susanne Erk, Chun Chieh Fan,
Iryna O. Fedko, Sonya F. Foley, Judith M. Ford, Masaki Fukunaga, Melanie E. Garrett, Tian Ge,
Sudheer Giddaluru, Aaron L. Goldman, Melissa J. Green, Nynke A. Groenewold, Dominik Gro tegerd,
Tiril P. Gurholt, Boris A. Gutman, Narelle K. Hansell, Mathew A. Harris, Marc B. Harrison, Courtney
C. Haswell, Michael Hauser, Stefan Herms, Dirk J. Heslenfeld, New Fei Ho, David Hoehn, Per
Hoffmann, Laurena Holleran, Martine Hoogman, Jouke-Jan Hottenga, Masashi Ikeda, Deborah Janowitz,
Iris E. Jansen, Tianye Jia, Christiane Jockwitz, Ryota Kanai, Sherif Karama, Dalia Kasperaviciute,
Tobias Kaufmann, Sinead Kelly, Masataka Kikuchi, Marieke Klein, Michael Knapp, Annchen R. Knodt,
Bernd Krämer, Max Lam, Thomas M. Lancaster, Phil H. Lee, Tristram A. Lett, Lindsay B. Lewis, Iscia
Lopes-Cendes, Michelle Luciano, Fabio Macciardi, Andre F. Marquand, Samuel R. Mathias, Tracy R.
Melzer, Yuri Milaneschi, Nazanin Mirza-Schreiber, Jose C. V. Moreira, Thomas W. Mühleisen, Bertram
Müller-Myhsok, Pablo Najt, Soichiro Nakahara, Kwangsik Nho, Loes M. Olde Loohuis, Dimitri
Papadopoulos Orfanos, John F. Pearson, Toni L. Pitcher, Benno Pütz, Yann Quidé, Anjanibhargavi
Ragothaman, Faisal M. Rashid, William R. Reay, Ronny Redlich, Céline S. Reinbold, Jonathan Repple,
Geneviève Richard, Brandalyn C. Riedel, Shannon L. Risacher, Cristiane S. Rocha, Nina R. Mota,
Lauren Salminen, Arvin Saremi, Andrew J. Saykin, Fenja Schlag, Lianne Schmaal, Peter R. Schofield,
Rodrigo Secolin, Chin Yang Shapland, Li Shen, Jean Shin, Elena Shumskaya, Ida E. Sønderby, Emma
Sprooten, Katherine E. Tansey, Alexander Teumer, Anbupalam Thalamuthu, Diana Tordesillas-
Gutiérrez, Jessica A. Turner, Anne Uhlmann, Costanza L. Vallerga, Dennis van der Meer, Marjolein M.
J. van Donkelaar, Liza van Eijk, Theo G. M. van Erp, Neeltje E. M. van Haren, Daan van Rooij, Marie -
José van Tol, Jan H. Veldink, Ellen Verhoef, Esther Walton, Mingyuan Wang, Yunpeng Wang, Joanna
M. Wardlaw, Wei Wen, Lars T. Westlye, Christopher D. Whelan, Stephanie H. Witt, Katharina Wittfeld,
Christiane Wolf, Thomas Wolfers, Jing Qin Wu, Clarissa L. Yasuda, Dario Zaremba, Zuo Zhang, Marcel
P. Zwiers, Eric Artiges, Amelia A. Assareh, Rosa Ayesa-Arriola, Aysenil Belger, Christine L. Brandt,
Gregory G. Brown, Sven Cichon, Joanne E. Curran, Gareth E. Davies, Franziska Degenhardt, Michelle
F. Dennis, Bruno Dietsche, Srdjan Djurovic, Colin P. Doherty, Ryan Espiritu, Daniel Garijo, Yolanda
Gil, Penny A. Gowland, Robert C. Green, Alexander N. Häusler, Walter Heindel, Beng-Choon Ho,
Wolfgang U. Hoffmann, Florian Holsboer, Georg Homuth, Norbert Hosten, Clifford R. Jack Jr., MiHyun
Jang, Andreas Jansen, Nathan A. Kimbrel, Knut Kolskår, Sanne Koops, Axel Krug, Kelvin O. Lim,
 Jurjen J. Luykx, Daniel H. Mathalon, Karen A. Mather, Venkata S. Mattay, Sarah Matthews, Jaqueline
Mayoral Van Son, Sarah C. McEwen, Ingrid Melle, Derek W. Morris, Bryon A. Mueller, Matthias
Nauck, Jan E. Nordvik, Markus M. Nöthen, Daniel S. O’Leary, Nils Opel, Marie-Laure Paillère
Martinot, G. Bruce Pike, Adrian Preda, Erin B. Quinlan, Paul E. Rasser, Varun Ratnakar, Simone
Reppermund, Vidar M. Steen, Paul A. Tooney, Fábio R. Torres, Dick J. Veltman, James T. Voyvodic,
Robert Whelan, Tonya White, Hidenaga Yamamori, Hieab H. H. Adams, Joshua C. Bis, Stephanie
Debette, Charles Decarli, Myriam Fornage, Vilmundur Gudnason, Edith Hofer, M. Arfan Ikram, Lenore
Launer, W. T. Longstreth, Oscar L. Lopez, Bernard Mazoyer, Thomas H. Mosley, Gennady V.
Roshchupkin, Claudia L. Satizabal, Reinhold Schmidt, Sudha Seshadri, Qiong Yang, Alzheimer’s
Disease Neuroimaging Initiative, CHARGE Consortium, EPIGEN Consortium, IMAGEN Consortium,
SYS Consortium, Parkinson’s Progression Markers Initiative, Marina K. M. Alvim, David Ames, Tim J.
Anderson, Ole A. Andreassen, Alejandro Arias-Vasquez, Mark E. Bastin, Bernhard T. Baune, Jean C.
Beckham, John Blangero, Dorret I. Boomsma, Henry Brodaty, Han G. Brunner, Randy L. Buckner, Jan
K. Buitelaar, Juan R. Bustillo, Wiepke Cahn, Murray J. Cairns, Vince Calhoun, Vaughan J. Carr, Xavier
Caseras, Svenja Caspers, Gianpiero L. Cavalleri, Fernando Cendes, Aiden Corvin, Benedicto Crespo-
Facorro, John C. Dalrymple-Alford, Udo Dannlowski, Eco J. C. de Geus, Ian J. Deary, Norman Delanty,
Chantal Depondt, Sylvane Desrivières, Gary Donohoe, Thomas Espeseth, Guillén Fernández, Simon E.
Fisher, Herta Flor, Andreas J. Forstner, Clyde Francks, Barbara Franke, David C. Glahn, Randy L.
Gollub, Hans J. Grabe, Oliver Gruber, Asta K. Håberg, Ahmad R. Hariri, Catharina A. Hartman, Ryota
Hashimoto, Andreas Heinz, Frans A. Henskens, Manon H. J. Hillegers, Pieter J. Hoekstra, Avram J.
Holmes, L. Elliot Hong, William D. Hopkins, Hilleke E. Hulshoff Pol, Terry L. Jernigan, Erik G.
Jönsson, René S. Kahn, Martin A. Kennedy, Tilo T. J. Kircher, Peter Kochunov, John B. J. Kwok,
Stephanie Le Hellard, Carmel M. Loughland, Nicholas G. Martin, Jean-Luc Martinot, Colm McDonald,
Katie L. McMahon, Andreas Meyer-Lindenberg, Patricia T. Michie, Rajendra A. Morey, Bryan Mowry,
Lars Nyberg, Jaap Oosterlaan, Roel A. Ophoff, Christos Pantelis, Tomas Paus, Zdenka Pausova, Brenda
W. J. H. Penninx, Tinca J. C. Polderman, Danielle Posthuma, Marcella Rietschel, Joshua L. Roffman,
Laura M. Rowland, Perminder S. Sachdev, Philipp G. Sämann, Ulrich Schall, Gunter Schumann, Rodney
J. Scott, Kang Sim, Sanjay M. Sisodiya, Jordan W. Smoller, Iris E. Sommer, Beate St Pourcain, Dan J.
Stein, Arthur W. Toga, Julian N. Trollor, Nic J. A. Van der Wee, Dennis van ’t Ent, Henry Völzke,
Henrik Walter, Bernd Weber, Daniel R. Weinberger, Margaret J. Wright, Juan Zhou, Jason L. Stein§*,
Paul M. Thompson§*, Sarah E. Medland§*, Enhancing NeuroImaging Genetics through Meta-Analysis
Consortium (ENIGMA)—Genetics working group

*Corresponding author. Email: katrina.grasby@qimrberghofer.edu.au (K.L.G.);

njahansh@usc.edu (N.J.); jason_stein@med.unc.edu (J.L.S.); pthomp@usc.edu (P.M.T.);
sarah.medland@qimrberghofer.edu.au (S.E.M.)

†These authors contributed equally to this work.

‡These authors contributed equally to this work.
§These authors contributed equally to this work.

Published 20 March 2020, Science 367, eaay6690 (2020)

DOI: 10.1126/science.aay6690

This PDF file includes:

Materials and Methods

Supplementary Text
Consortium Authors
Additional Cohort Information
Supplementary Acknowledgements
Figs. S1 and S6 to S10
Captions for Figs. S2 to S5 and S11
Captions for Tables S1 to S20
References
Other Supplementary Material for this manuscript includes the following:
(available at science.sciencemag.org/content/367/6484/eaay6690/suppl/DC1)

Figs. S2 to S5 and S11 (.pdf)

Tables S1 to S20 (.xlsx)

Correction: See Erratum at science.org/doi/10.1126/science.abm7211.

Contents
Materials and Methods .................................................................................................................... 5
Supplementary Text ...................................................................................................................... 13
Consortium Authors ...................................................................................................................... 14
Additional Cohort Information ..................................................................................................... 24
Supplementary Acknowledgements.............................................................................................. 26
Fig. S1. .......................................................................................................................................... 31
Fig. S2. (see external file ManhattanPlots.pdf)............................................................................. 32
Fig. S3. (see external fileQQPlots.pdf) ......................................................................................... 33
Fig. S4. (see external file Forest Plots.pdf). .................................................................................. 34
Fig. S5. (see external file LocusZoom.pdf). ................................................................................. 35
Fig. S6. .......................................................................................................................................... 36
Fig. S7. .......................................................................................................................................... 37
Fig. S8. .......................................................................................................................................... 38
Fig. S9. .......................................................................................................................................... 39
Fig. S10. ........................................................................................................................................ 40
Fig. S11. (see external file PhenotypicPlots.pdf) .......................................................................... 41
Tables S1 to S20 (separate file Grasby_etal_Supplementary_Tables.xlsx). ................................ 42

4
Materials and Methods
Imaging
Measures of cortical surface area (SA) and thickness (TH) were derived from in vivo whole brain
T1-weighted magnetic resonance imaging (MRI) scans using FreeSurfer MRI processing software
(1) (table S3). SA and TH were quantified for each subject within 34 distinct gyral-defined regions
in each brain hemisphere according to the Desikan-Killiany atlas (10) (Fig. 1A). SA was measured
at the grey-white matter boundary. TH was measured as the average distance between the white
matter and pial surfaces. The total SA and average TH of each hemisphere was computed
separately. High test-retest correlations have been previously reported for all measures with the
exception of the frontal and temporal poles (7). Image processing and quality control were
implemented at the cohort level following detailed, harmonized protocols.

Site analysts visually inspected the 34 bilateral cortical Desikan-Killiany atlas segmentations for
each subject. Visual inspection was conducted to assess extraction of the cortical grey matter
ribbon, to identify regional boundary errors on the cortical surface, and ensure the accuracy of
anatomical labels. Inspection was slice by slice on an orthogonal view, as well as on the external
surface view. Regions marked as “failed segmentations” were excluded from analyses. SA and TH
estimates beyond 2.698 SD from the mean were flagged in order to be more carefully inspected
by the respective site analysts. A quantitative assessment of quality was not applied; subjects or
regions were marked either as acceptable or not by a human rater. As this was a binary “pass” or
“fail” flag for each region, no additional metrics were added to the statistical analysis at the site
level. For sites that removed subjects for only the region that failed, the number of subjects
available varied across regions. For sites that removed subjects entirely for regional fails, the total
number of subjects available was the same as for all regions. We also note that some cohorts
removed poor quality scans from their database, so for some cohorts the number of quality control
issues may be limited. We include the percent of regional data available at the cohort-level in table
S3. The protocols that were used for the imaging quality control are available online from the
ENIGMA website (http://enigma.ini.usc.edu/protocols/imaging-protocols).

Phenotype distributions for all traits in all cohorts were inspected centrally prior to meta-analysis
(fig. S11). Any cohort where the phenotypic distribution for a given trait showed deviation from
expectations that could not be resolved through re-analysis or outlier inspection were excluded
from analyses of that trait.

Genome-wide association analyses

At each site, genotypes were imputed using either the 1000 Genomes Project (70) or Haplotype
Reference Consortium (71) references (table S4). To ensure consistency in the correction for
ancestry and stability of the correction given the relatively small sample sizes, each cohort also
ran the same multidimensional scaling (MDS) analysis protocol in which the data from the
HapMap 3 populations were merged with the site level data and MDS components were calculated
across this combined data set. Within each cohort, genome-wide association (GWAS) was
conducted using an additive model including covariates to control for the effects of age, age2, sex,
sex-by-age and age2 interactions, ancestry (the first four MDS components), diagnostic status
(when the cohort followed a case-control design), and dummy variables for scanner (when multiple
scanners were used at the same site).

5
The primary GWAS of regional measures included the global measure of SA or TH as an
additional covariate, to test for genetic influences specific to each region. However, to aid
interpretation, the regional GWAS were also run without controlling for global measures. Cohort
level GWAS results underwent quality control (excluding variants with an imputation R2 ≤ 0.5 and
MAF ≤ 0.005). Across all cohorts, for each phenotype, GWAS summary plots (Manhattan and QQ
plots) were visually inspected by the central analysis group; if a given trait showed deviation from
expectations that could not be resolved through re-analysis, then that cohort was excluded from
analyses of that trait.

Meta-analysis
The initial meta-analysis was conducted on all of the ENIGMA European cohorts with genome-
wide imputed data, and was then meta-analyzed with the UK Biobank European participants to
give the principal results. For replication, we took forward the significant variants from the
principal results and meta-analyzed them with an additional ENIGMA cohort and results from the
CHARGE consortium. We also extracted these variants from a meta-analysis of non-European
cohorts to examine generalization of effects across ancestry. Cohort information is provided in
table S2. All meta-analyses were conducted using METAL (63). The results of the meta-analyses
are summarized in table S5. For the initial and principal meta-analyses we used standard error
weighted meta-analyses. In the replication steps we used sample size weighted meta-analyses, in
order to include results from the CHARGE consortium for which only sample size weighted results
were available. An additional ENIGMA cohort was also included in the sample size weighted
meta-analysis because the GWAS was conducted using a program that provided results on an
inverse normalized scale. For each meta-analysis, the results were quality controlled, removing
strand ambiguous SNPs and INDELs where the effect allele frequency crossed 0.5, and (for the
initial meta-analysis) variants where the total sample size was < 10,000. Independent loci were
identified by clumping significant loci in PLINK (72), with thresholds of 1 Mb and r2 < 0.2. For
the chromosome 17 inversion region this was increased to 10 Mb. For clumping, a random sample
of 5,000 unrelated individuals (plink 1.90 genetic relatedness ≤ 0.025) of European ancestry from
the UK Biobank were used as an LD reference.

Following Rietveld et al. (73), we estimated the variance explained R2 by each variant j as:
2
2𝑝𝑗 𝑞𝑗 . 𝛽̂𝑗2
𝑅𝑗 ≈
𝜎̂𝑦2
where pj and qj are the minor and major allele frequencies, 𝛽̂𝑗 is the estimated effect of the variant
within the meta-analysis and 𝜎̂𝑦2 is the estimated variance of the trait (for which we used the pooled
variance of the trait across all ENIGMA cohorts and UK Biobank; see table S1). To obtain beta
and standard error estimates from the results from the sample size weighted meta-analyses reported
in table S5 we used the following equations from Rietveld et al. (73):
𝜎̂𝑦 𝑧𝑗
𝛽̂𝑗 ≈ 𝑧𝑗 ∙ 𝑎𝑛𝑑 𝑆𝐸(𝛽̂𝑗 ) ≡
√𝑁𝑗 ∙ 2𝑝𝑗 𝑞𝑗 𝛽̂𝑗
Where zj is the Z-score and SE (𝛽̂𝑗 ) is the estimated standard effect of the variant within the meta-
analysis and N is the number of contributing alleles.

6
Multiple testing correction
We analyzed 70 traits (total SA, average TH, and the SA and TH of 34 cortical regions averaged
across right and left hemispheres). However, after accounting for the correlation between the traits
in the UK Biobank (residuals correcting for sex, age, ancestry and global measures) using matrix
spectral decomposition (12), the effective number of traits was estimated to be 60. Therefore, we
applied the significance threshold of P ≤ 8.3 x 10-10 to correct for multiple testing in the GWAS
meta-analysis results. Multiple testing corrections applied to each of the follow-up analyses are
described below.

Analyses of UK Biobank data

Analyses of the UK Biobank cohort were conducted on the 2018 (version 3) imputed genotypes,
imputed to the Haplotype Reference Consortium and merged UK10K and 1000 Genomes (phase
3) panels. UK Biobank bulk imaging data were made available for 12,962 individuals under
application #11559 in July 2017, with data from an additional 5,095 individuals made available in
August 2019. We processed the raw MRI data using the ENIGMA protocols described above.
Following processing, all images were visually inspected. Analyses of UK Biobank participants
within 0.02 on the first and second MDS components of the European centroid were included in
the meta-analyses of the European ancestry cohorts. Analyses of participants beyond this threshold
were included in the meta-analysis of non-European ancestry cohorts.

Gene-based association analyses

We conducted genome-wide gene-based association analysis using the principal meta-analytic
results. We used the 19,427 protein-coding genes from the NCBI 37.3 gene definitions as the basis
for the gene-based association analysis using MAGMA (67). For each gene we selected all SNPs
within exonic, intronic and untranslated regions as well as SNPs within 50 kb upstream and
downstream of the gene. After SNP annotation, there were 18,048 genes that were covered by at
least one SNP. Gene-based association tests were performed taking LD between SNPs into
account. We applied a Bonferroni correction to account for multiple testing, adjusting for the
number of genes tested as well as the effective number of traits tested (60 independent traits),
setting the genome-wide threshold for significance at 4.5 x 10−8. These results are shown in table
S6.

Twin heritability
Twin heritability was estimated in the ENIGMA Queensland Twin Imaging (QTIM) study of
healthy adolescent and young adult twins and their siblings (N = 923; 157 MZ pairs, 194 DZ pairs,
221 unpaired twins) using OpenMx (74) in R. Structural equation models were fitted to total SA,
average TH, and the SA and TH of 34 cortical regions averaged across right and left hemispheres
using full information maximum likelihood to decompose the variance into additive genetic and
environmental factors. The models included a simultaneous means regression to adjust for effects
of sex, linear and nonlinear age effects, interactions between age and sex, MRI acquisition
orientation, and for the regional measures we analyzed a version with and one without the
corresponding global measures. We performed analyses without controlling for global measures
for completeness. The likelihood ratio test was used to select the best fitting most parsimonious
model, which was a model explaining the phenotypic differences in variance by additive genetic
factors and unique environmental factors (including measurement error). These results are shown
in table S7.

7
Heritability due to common variants
For each of the 70 traits, we used LD score regression (64, 65) to estimate the proportion of
variance accounted for by common SNPs or SNP heritability (h2SNP). These results are shown in
table S7.

Partitioned heritability
Partitioned heritability analysis was used to estimate the percentage of heritability explained by
annotated regions of the genome (66). Annotations were derived from either Epigenomics
Roadmap (22) or a study of chromatin accessibility in mid-fetal brains (21). For analyses using
Epigenomics Roadmap data, ChromHMM chromatin states (15 state model) were downloaded for
available tissue types (http://egg2.wustl.edu/roadmap/web_portal/chr_state_learning.html). For
each tissue, genomic regions comprising all active regulatory elements (TssA, TssAflnk, Enh,
EnhG) within each tissue type were added as an additional annotation to the baseline model
provided with the LDSC package (https://github.com/bulik/ldsc). A separate analysis was
conducted by identifying if the same active regulatory elements that were specific to either fetal
brain (combining annotations from BRN.FET.F and BRN.FET.M) or adult brain cortex
(combining annotations from BRN.CING.GYR, BRN.INF.TMP, BRN.ANG.GYR,
BRN.DL.PRFRNTL.CRTX). Those elements present in fetal brain showing no overlap with adult
brain cortex were used as “fetal brain specific”. Conversely, those elements present in adult brain
cortex showing no overlap with fetal brain were used as “adult brain specific”. These annotations
were added separately to the baseline model. For analyses using chromatin accessibility in mid-
fetal brains, the genomic coordinates of peaks more accessible in the germinal zone than the
cortical plate (GZ > CP) and peaks more accessible in the cortical plate than the germinal zone
(CP > GZ) were added jointly to the baseline annotations. A separate analysis was conducted
subsetting to chromatin accessibility peaks defined in fetal brain that showed evidence of
regulating cell-type specifically expressed genes in mid-fetal development. Cell-type definitions
and genes with cell-type specific expression (log2 fold change > 0.2 between cell-types, BH
corrected P < 0.05, Expressed in 10% of cells in cluster) were acquired from previously published
work (23). Peaks near the TSS of cell-type specific genes (promoter peaks) and those with
significant chromatin accessibility correlation with promoter peaks were used as cell-type specific
annotations. These annotations of all 16 cell-types were added to the baseline model. Partitioned
heritability and the enrichment of heritability explained in these annotations was run using LD
score regression (66). The significance of enrichment was corrected across all annotations
displayed in each of the analyses using FDR correction (FDR ≤ 0.05) and the significance and
enrichment scores were plotted (Fig. 2B–D, fig S6A–D).

Genetic and phenotypic correlations and clustering of genetic correlations

LD score regression (64) was also used to estimate genetic correlations between cortical regions
and with global measures. These results are shown in table S14−15. Phenotypic correlations were
calculated from the UK Biobank cohort (residuals correcting for sex, age, ancestry, and global
brain measures). We used a threshold of P ≤ 8.3 x 10-4 (0.05/60) to correct for multiple testing in
the genetic and phenotypic correlations shown in Fig. 3.

To identify patterns of genetic correlations of SA and TH (both with and without correction for
global measures), we used Mclust (75) for hierarchical cluster analysis, which uses expectation-

8
maximization to fit parameterized Gaussian mixture models to the data. The best-fitting model for
number and shape of clusters was selected as the one with the largest Bayesian Information
Criterion. These results are shown in fig. S9.

Genetic correlations were calculated to determine if shared genetic influences contributed to both
cortical structure and neuropsychiatric disorders or psychological traits. Summary statistics were
downloaded from the following published genome-wide association studies: general cognitive
function (54), insomnia (55), antisocial behavior (76), educational attainment (28), subjective well-
being (57), depressive symptoms (57), neuroticism (29), attention deficit hyperactivity disorder
(ADHD; 56), autism (77), bipolar disorder (78), anorexia nervosa (79), major depressive disorder
(58), obsessive compulsive disorder (80), post-traumatic stress disorder (PTSD; 81), schizophrenia
(82), anxiety disorders (83), aggression (84), Alzheimer's disease (85), loneliness (86), cigarettes
smoked per day (87), epilepsy (88), Parkinson's disease (27), and frontotemporal dementia (69).
LD score regression was used to calculate genetic correlations (64). Significance was corrected for
multiple comparisons using FDR across all genetic correlations with average TH and total SA, and
significant associations were highlighted in Fig. 5A. To explore regional variability in those
significant genetic correlations, genetic correlations were conducted between the trait and the
cortical regions (without correcting for global measures) are depicted in Fig. 5B.

Polygenic risk score analyses

To examine the extent to which our analyses could predict SA and TH in an independent dataset,
we derived polygenic risk scores (PRS) from the primary meta-analysis results. Using data from
an additional 5,095 unrelated individuals of European ancestry from the UK Biobank who were
unrelated to participants who contributed to the meta-analysis (plink 1.90 genetic relatedness ≤
0.025). The index variants used to weight the PRS were identified by clumping the meta-analytic
results in plink 1.90 using an r2 threshold of 0.1 with a 1000 kb window using the genotypic data
of the prediction cohort as a reference. Following checks for strand alignment, PRS were calculated
using the probabilistic imputed genotype dosages to account for imputation uncertainty. PRS were
calculated for P-value thresholds of P ≤ 5 x 10-8, 1 x 10-5, 0.001, 0.01, 0.05, 0.1, 0.5, 1. The
proportion of variance accounted for by a given PRS was estimated by comparing the R2 of a linear
regression analysis that included the PRS and the covariates that were included in the GWAS
analyses to a corresponding analysis that only included the covariates (conducted in R lm). The
results of these analyses are presented in table S7.

Mendelian randomization and latent causal variant analyses

We performed 2-sample Mendelian randomization (2SMR) and latent causal variant (LCV)
analyses to investigate whether significant correlations detected by the analyses above could be
driven by causal genetic relationships between an exposure (e.g., total surface area) and an
outcome (e.g. the correlated traits). The 2SMR analyses were performed using MR-Base (59),
which performs a series of MR and sensitivity analyses to evaluate evidence for causality and
detect the presence of horizontal pleiotropy (where a SNP directly influences an outcome, violating
the MR assumption that SNPs only influence the outcome through their effect on the exposure),
and MR-PRESSO (89), which detects and then corrects for horizontal pleiotropy by removing
SNPs with outlying effects on the outcome trait. For each exposure trait, we included only SNPs
GWAS P-values < 5.0 x 10-8 which were clumped for LD (r2 < 0.01) to ensure only significantly
exposure-associated, independent variants were included as the instrumental variables. SNP

9
effects were standardized prior to analysis. We conservatively set the threshold for significance at
P = 3.13 x 10-3 (0.05/16 trait comparisons). Where there was significant evidence of SNP
heterogeneity in effect sizes for outcome traits the analyses were re-run in MR-Base with the
outlier SNPs removed as further sensitivity analyses to determine the extent to which the
relationship between traits was influenced by the outlier SNPs. The results of the MR analyses are
presented in table S18. We present the betas and their standard errors for the two associated
quantitative traits in the main text following sensitivity analyses suggesting all included
instruments (SNPs) were unbiased (59). Additionally, we show odds ratios and 95% confidence
intervals reflecting risk per standard deviation increase in the relevant exposure calculated from
the inverse variance weighted MR model result in table S18.

A key assumption of MR is that the genetic variants included in the analysis are specific
instruments for the exposure under investigation: false positive results can occur in the presence
of genetic correlation if the correlation is driven by pleiotropy (19, 90). Additionally, the exposure
trait (and also the outcome trait where a causal relationship exists) is likely to be affected by
residual genetic variation that doesn’t surpass the genome-wide significance threshold. To
overcome these potential limitations we also performed latent causal variable analyses using LCV-
Master (19). The LCV method mediates genetic correlation through the use of a latent variable
that has a causal effect on each trait. The degree of causality of a trait (trait 1) on another (trait 2)
is quantified using a genetic causality proportion (gcp) that ranges from -1 to 1, with gcp > abs(0.6)
implying full or nearly full genetic causality (19). All LCV analyses were performed using
genome-wide GWAS summary results (Z-scores) using the default settings. As LCV-Master
includes tests for causality in both directions the threshold for significance for these analyses was
set at P = 6.25 x 10-3 (0.05/8 trait comparisons). The LCV results are presented in table S19.

Multivariate GWAS analysis

We used TATES (42) to conduct two multivariate analyses: one for the 34 regional SA measures,
and a separate analysis for the 34 regional TH measures. These analyses were run on the meta-
analytic results from the second phase of meta-analysis. Briefly, TATES combines the P-values
from univariate GWAS while correcting for the phenotypic correlations between traits and does
not require access to raw genotypic data (42). The power of TATES has been shown to be similar
or greater than that of multivariate tests using raw data across a range of scenarios for analyses of
20 or more traits (91). For these analyses, we used phenotypic correlations calculated from the UK
Biobank cohort (residuals correcting for sex, age, ancestry, and global cortical measures).

Gene-set enrichment analyses

Gene-set enrichment analyses were performed on total SA and average TH as well as the
multivariate GWAS results for SA and TH using DEPICT (25). Within DEPICT, groups of SNPs
were assessed for enrichment in 14,462 gene-sets. These analyses were run using variants with P
≤ 1.0 x 10-5. Gene-set enrichment analyses were considered significant if they survived FDR
correction (q ≤ 0.05) (25). These results are shown in table S10.

Functional annotation
Potential functional impact was investigated for lead variants and their proxies (defined here as r2
> 0.6 to the lead SNP) at each of the 369 loci nominally associated with global and regional SA

10
and TH using a number of publicly available data sources. The majority of the SNP annotations
were as provided by FUMA (30) which annotates:
● SNP location (e.g., genic/intergenic)
● the potential for functional effects through predicted effects as determined by CADD (92)
and Regulome (93)
● expression quantitative trait (eQTL) effects. We considered eQTLs within cortical
structures from GTEx v7 (94), the UK Brain Expression Consortium (95), the
CommonMind Consortium (96), and PsychENCODE (97).
● the presence of enhancers and promoters in SNP regions (RoadMap tissues E053, E073,
E081, E082, E125)
● chromatin state and interactions in numerous brain tissues (GEO GSE87112). We included
data for dorsolateral prefrontal cortex and neural progenitor cells, PsychENCODE, and
adult and fetal cortex (98).
These data were used by FUMA to map coding and non-coding (e.g. lncRNA) genes to each lead
SNP and high LD proxies based on an eQTL effect with FDR-corrected P-values ≤ 0.05 in cortical
tissue and/or chromatin interactions between the region harboring the lead SNP and a gene
promoter in a second chromosomal region (including interactions with an FDR correction ≤ 1 x
10-6) (30). Default FUMA settings were used. In the main text we indicate the FDR values for
significant eQTL effects (i.e. FDR Q ≤ 0.05: both the nominal P-values and the FDR-corrected
values are provided in table S12). FDR values for adult eQTL data from GTEx reported in text as
FDRGTEx were derived from beta distribution-adjusted empirical P-values of nominal P-values
from t-tests of Pearson product-moment correlation coefficients that were FDR corrected using the
Storey Tibshirani method (30, 94). FDR values for adult eQTL data from the CommonMind
Consortium (CMC) reported in text as FDRCMC were derived from linear regression coefficient t-
tests that were FDR corrected and accessed by FUMA in Q-value bins (e.g. Q < 1.0 x 10-2). These
bin values are reported as whole numbers by FUMA (e.g. the Q < 1.0 x 10-2 bin is reported as Q =
9.0 x 10-3). We report the CMC bin value in the main text, although table S12 (FUMA “gene”
output) reports the corresponding FUMA-assigned values. For rs1080066, we also investigated if
it was reported as an eQTL in adult blood (99), the FDR value reported in text as FDRBIOSgenelevel
was derived from meta-analytic Z-scores and FDR corrected against permuted data. Fetal eQTL
data were taken from O’Brien et al (34). FDR values for fetal eQTLs reported in text as FDRFETAL
were derived from nominal P-values from t-tests of Pearson product-moment correlation
coefficients reported in the original paper that were FDR corrected for our significant loci using
the Benjamini-Hochberg method. HaploReg (100) was used to annotate transcription factor
binding across multiple tissues, and whether SNPs modified transcription factor binding motifs.
The potential for a detrimental effect on protein function due to lead or proxy SNPs located within
gene exons was investigated using SIFT and PolyPhen as reported by SNPNexus (40).

In Fig. 4A we annotate the genomic context of rs1080066 and high LD proxies associated with
additional traits, chromatin state in relevant tissues, and gene expression in pre- and post-natal
brains. Chromatin state represents the degree to which 200 bp genomic regions are accessible for
transcription. Around each of our associated loci chromatin state was annotated by FUMA (30)
utilizing the core 15-state model (table S11). In Fig. 4A, genomic regions in three tissues/cells
most relevant to our study (RoadMap E073 dorsolateral prefrontal cortex [Adult cortex], E081
female fetal brain [Fetal brain], and E125 NH-A Astrocytes Primary Cells [Astrocytes]) are
indicated as one of the 15 possible chromatin states as predicted by Roadmap Epignomics using

11
ChromHMM, based on data for 5 chromatin marks (H3K4me3, H3K4me1, H3K36me3,
H3K27me3, H3K9me3) in 127 epigenomes (22). Chromatin states are as follows: TssA:Active
Transcription Start Site (TSS); TssAFlnk:Flanking Active TSS; TxFlnk:Transcription at gene 5'
and 3'; Tx:Strong transcription; TxWk:Weak transcription; EnhG:Genic enhancers;
Enh:Enhancers; ZNF/Rpts:ZNF genes & repeats; Het:Heterochromatin; TssBiv:Bivalent/Poised
TSS; BivFlnk:Flanking Bivalent TSS/Enhancer; EnhBiv:Bivalent Enhancer; ReprPC:Repressed;
PolyComb; ReprPCWk:Weak Repressed PolyComb; Quies:Quiescent/Low. Pre- and post-natal
gene expression data across multiple brain regions was obtained from the BrainSpan Atlas of the
Developing Human Brain (http://www.brainspan.org/). These data include gene expression
information for cortical tissues indicated on a scale from low (dark blue) to high (dark red)
expression on a log2 RPKM scale (RPKM = Reads Per Kilobase [of transcript per] Million
[mapped reads], which normalizes expression levels to account for sequencing depth and gene
length). The BRAINSPAN cortical tissues, organised in ontological order, are as follows:
DFC:dorsolateral prefrontal cortex; VFC:ventrolateral prefrontal cortex; MFC:anterior (rostral)
cingulate (medial prefrontal) cortex; OFC:orbital frontal cortex; M1C:primary motor cortex (area
M1, area 4); M1C-S1C:primary motor-sensory cortex (samples); PCx:parietal neocortex;
S1C:primary somatosensory cortex (area S1, areas 3,1,2); IPC:posteroventral (inferior) parietal
cortex; A1C:primary auditory cortex (core); TCx:temporal neocortex; STC:posterior (caudal)
superior temporal cortex (area 22c); ITC:inferolateral temporal cortex (area TEv, area 20);
Ocx:occipital neocortex; V1C:primary visual cortex (striate cortex, area V1/17).

For each locus, we evaluated functional annotations for the lead SNP and for additional SNPs
considered to be credible causal variants (CCVs) if they were either i) in reasonable LD (r2 ≥ 0.6
in individuals of European ancestry) with the lead SNP and/or ii) had P-values within 2 orders of
magnitude of the lead SNP. As lincRNAs show considerable cell/tissue specificity, in the main
text we detail SNP location based on neighboring coding genes, but detail lincRNAs when our
lead SNPs show eQTL effects and/or chromatin interactions to these non-coding transcripts. Genes
at each associated locus were determined to be potential candidates by considering whether the
lead SNP (or a proxy) was an eQTL for a particular gene in adult or fetal cortical tissue (listed
above) and/or when chromatin interactions were observed to occur between the region harboring
the lead/proxy SNPs and a gene promoter in relevant brain tissues (dorsolateral prefrontal cortex
and/or neural progenitor cells).

Analysis of the central sulcus

To follow-up the precentral surface area association with rs1080066, 10,557 UK Biobank MRI
scans were further analyzed using BrainVISA-4.5 Morphologist pipeline for the extraction and
parameterization of the central sulcus. Quality controlled FreeSurfer outputs (orig.mgz,
ribbon.mgz and talairach.auto) were directly imported into the pipeline to use the same grey and
white matter segmentations. Sulci were automatically labeled according to a predefined anatomical
nomenclature of 61 sulcal labels per hemisphere (101, 102). Extracted meshes for the left and right
central sulcus were visually quality checked; subjects with mislabeled central sulcus were
discarded from further analysis; 6,045 individuals had good quality extractions for both the left
and right hemispheres. An additional 52 individuals were removed for genotyping quality or
ancestry reasons. The central sulcus depth profile was measured by extending the method
introduced in Cykowski et al. (47) and Hopkins et al. (103). The ridges at the fundus of the sulcus
and at the convex hull, along with the two extremities, were automatically extracted. Using these

12
landmarks, two coordinate fields (x and y) were extrapolated over the entire mesh surface (104).
Sulcal depth was defined as the distance between paired points at the sulcal fundus and brain
envelope that shared the same y coordinate (105). For each individual, the parametrized surface
was divided into 100 equally spaced points along the length of the sulcus, and the depth at each
point was recorded for comparison. We averaged the corresponding depth measurements across
the left and right sulcus and calculated the effect of the rs1080066 G allele on the bilaterally
averaged depth at each point. These results are shown in Fig. 4D.

Fine mapping
In order to identify putatively causal variants at each associated locus for future functional
validation experiments, we performed fine-mapping with CAVIAR (68). For each associated locus
(defined in table S5), all SNPs with r2 > 0.6 (using 1000G EUR reference panel) to the index SNP
for that locus and P < 0.001 to the brain trait of interest were input into the CAVIAR program
(v2.2). CAVIAR was then run for each locus specifying two causal variants per locus and using
LD patterns from 1000G EUR reference panel to identify the set of SNPs that have a 95%
probability of containing the causal variants. These are output in table S13. For those loci where
the index SNP was not found in 1000G data, only the index SNP was identified as putatively
causal.

Supplementary Text
The Desikan-Killiany atlas
The Desikan-Killiany atlas (10) used here to define the 34 regions of interest is one of many
possible atlases. This atlas was chosen as it is a common output of FreeSurfer, and it is one of the
coarser atlases, yielding larger, more consistent regions, defined by the common folding patterns
visible on standard MRI. More recent efforts partitioning the cortex into 180 regions have used
high-resolution multimodal assessments (MMPC; 106). Other atlases based on functional
partitions have also been used, particularly for analyzing function MRI data (107, 108). The
breakdown of the cortical surface into 34 large parcels yields clear boundaries between the regions,
and allows for anatomically driven quality assessments (see Imaging in the Supplementary
Materials and Methods).

The choice of atlas will not have an effect on the global measures; however, the choice of atlas
would influence our regional findings, and possibly limit findings, as we may not be able to detect
genetic influences on functionally coherent cortical regions, or refined cortical regions partitioned
by multimodal MRI measures, for example myelin content, which may have more pathway-
specific genetic influences. Assessing the genetic influences on the cortex at a finer scale is an
important future effort. However, for multi-cohort efforts such as that performed here, the
reliability and accuracy of the parcellations should be assessed across multiple age ranges and MRI
acquisition parameters, such as field strength. Automated, and reliable, quality assurance and label
accuracy assessments would be an important aspect of this next step.

Our choice of atlas is also likely to influence our findings of regional genetic correlations. It is
possible that the correlations between adjacent structures, seen in our analysis, may reflect
suboptimal partitioning of the cortex by the atlas; for example, we see a positive genetic correlation
between the inferior parietal and the superior parietal gyri, whereas in the MMPC atlas, a portion

13
of each of these two regions is included under a new label, the intraparietal label. Portions of these
genetically correlated regions may be re-assigned based on other advanced imaging data, such as
multimodal myelin mapping, which may better define cortical cellular architecture.

Sulcal development
Positive genetic correlations between the SA of neighboring regions may also be driven by the
development of the sulcus, separating the regions. The pre- and post- central regions (also known
as the primary motor and sensorimotor cortices, respectively) are consistently labeled across many
cortical atlases as the regions directly anterior and posterior to the central sulcus, which appears
early in development (109). The SA of all four regions surrounding the calcarine sulcus (the
pericalcarine, lingual, cuneus, and lateral occipital region) show positive genetic correlations. The
same is also true for the SA of the insula and superior temporal gyri surrounding the lateral sulcus
(or Sylvian fissure). These major, early-forming sulci show positive genetic correlations between
the regions that directly surround them for SA, but not TH. These observations may imply that
part of the genetic influences we observe to be underlying regional SA, may actually be driving
the formation of the separating folds, or sulci, during fetal development.

Consortium Authors
Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Data used in preparing this article were obtained from the Alzheimer’s Disease Neuroimaging
Initiative (ADNI) database (adni.loni.usc.edu). As such, many investigators within the ADNI
contributed to the design and implementation of ADNI and/or provided data but did not participate
in analysis or writing of this report. A complete listing of ADNI investigators may be found at:
http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.
ADNI Infrastructure Investigators: Michael Weiner (UC San Francisco), Paul Aisen (University
of Southern California), Ronald Petersen (Mayo Clinic, Rochester), Clifford R. Jack, Jr. (Mayo
Clinic, Rochester), William Jagust (UC Berkeley), John Q. Trojanowki (U Pennsylvania), Arthur
W. Toga (USC), Laurel Beckett (UC), Davis Robert C. Green (Brigham and Women’s
Hospital/Harvard Medical School), Andrew J. Saykin (Indiana University), John Morris
(Washington University St. Louis), Leslie M. Shaw (University of Pennsylvania). ADNI External
Advisory Board (ESAB): Zaven Khachaturian (Prevent Alzheimer’s Disease 2020 (Chair)), Greg
Sorensen (Siemens), Maria Carrillo (Alzheimer’s Association), Lew Kuller (University of
Pittsburgh), Marc Raichle (Washington University St. Louis), Steven Paul (Cornell University),
Peter Davies (Albert Einstein College of Medicine of Yeshiva University), Howard Fillit (AD
Drug Discovery Foundation), Franz Hefti (Acumen Pharmaceuticals), David Holtzman
(Washington University St. Louis), M. Marcel Mesulam (Northwestern University), William
Potter (National Institute of Mental Health), Peter Snyder (Brown University). ADNI 3 Private
Partner Scientific Board (PPSB): Veronika Logovinsky, (Eli Lilly (Chair)). Data and Publications
Committee: Robert C. Green (BWH/HMS (Chair)). Resource Allocation Review Committee: Tom
Montine (University of Washington (Chair)). Clinical Core Leaders: Ronald Petersen (Mayo
Clinic, Rochester (Core PI)), Paul Aisen (University of Southern California). Clinical Informatics
and Operations: Gustavo Jimenez (USC), Michael Donohue (USC), Devon Gessert (USC), Kelly
Harless (USC), Jennifer Salazar (USC), Yuliana Cabrera (USC), Sarah Walter (USC), Lindsey
Hergesheimer (USC). Biostatistics Core Leaders and Key Personnel: Laurel Beckett (UC Davis
(Core PI)), Danielle Harvey (UC Davis), Michael Donohue (UC San Diego). MRI Core Leaders

14
and Key Personnel: Clifford R. Jack, Jr. (Mayo Clinic, Rochester (Core PI)), Matthew Bernstein
(Mayo Clinic, Rochester), Nick Fox (University of London), Paul Thompson (UCLA School of
Medicine), Norbert Schuff (UCSF MRI), Charles DeCarli (UC Davis), Bret Borowski (RT Mayo
Clinic), Jeff Gunter (Mayo Clinic), Matt Senjem (Mayo Clinic), Prashanthi Vemuri (Mayo Clinic),
David Jones (Mayo Clinic), Kejal Kantarci (Mayo Clinic), Chad Ward (Mayo Clinic). PET Core
Leaders and Key Personnel: William Jagust (UC Berkeley (Core PI)), Robert A. Koeppe
(University of Michigan), Norm Foster (University of Utah), Eric M. Reiman (Banner Alzheimer’s
Institute), Kewei Chen (Banner Alzheimer’s Institute), Chet Mathis (University of Pittsburgh),
Susan Landau (UC Berkeley). Neuropathology Core Leaders: John C. Morris (Washington
University St. Louis), Nigel J. Cairns (Washington University St. Louis), Erin Franklin
(Washington University St. Louis), Lisa Taylor-Reinwald (Washington University St. Louis – Past
Investigator). Biomarkers Core Leaders and Key Personnel: Leslie M. Shaw (UPenn School of
Medicine), John Q. Trojanowki (UPenn School of Medicine), Virginia Lee (UPenn School of
Medicine), Magdalena Korecka (UPenn School of Medicine), Michal Figurski (UPenn School of
Medicine). Informatics Core Leaders and Key Personnel: Arthur W. Toga (USC (Core PI)), Karen
Crawford (USC), Scott Neu (USC). Genetics Core Leaders and Key Personnel: Andrew J. Saykin
(Indiana University), Tatiana M. Foroud (Indiana University), Steven Potkin (UC Irvine), Li Shen
(Indiana University), Kelley Faber (Indiana University), Sungeun Kim (Indiana University),
Kwangsik Nho (Indiana University). Initial Concept Planning & Development: Michael W.
Weiner (UC San Francisco), Leon Thal (UC San Diego), Zaven Khachaturian (Prevent
Alzheimer’s Disease 2020). Early Project Proposal Development: Leon Thal (UC San Diego),
Neil Buckholtz (National Institute on Aging), Michael W. Weiner (UC San Francisco), Peter J.
Snyder (Brown University), William Potter (National Institute of Mental Health), Steven Paul
(Cornell University), Marilyn Albert (Johns Hopkins University), Richard Frank (Richard Frank
Consulting), Zaven Khachaturian (Prevent Alzheimer’s Disease 2020). NIA: John Hsiao (National
Institute on Aging). ADNI Investigators by Site: Oregon Health & Science University: Joseph
Quinn, Lisa C. Silbert, Betty Lind, Jeffrey A. Kaye – Past Investigator, Raina Carter – Past
Investigator, Sara Dolen – Past Investigator. University of Southern California: Lon S. Schneider,
Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann – Past Investigator.
University of California – San Diego: James Brewer, Helen Vanderswag, Adam Fleisher – Past
Investigator. University of Michigan: Jaimie Ziolkowski, Judith L. Heidebrink, Joanne L. Lord –
Past Investigator. Mayo Clinic, Rochester: Ronald Petersen, Sara S. Mason, Colleen S. Albers,
David Knopman, Kris Johnson – Past Investigator. Baylor College of Medicine: Javier Villanueva-
Meyer, Valory Pavlik, Nathaniel Pacini, Ashley Lamb, Joseph S. Kass, Rachelle S. Doody – Past
Investigator, Victoria Shibley – Past Investigator, Munir Chowdhury – Past Investigator, Susan
Rountree – Past Investigator, Mimi Dang – Past Investigator. Columbia University Medical
Center: Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Randy Yeh. Washington University, St.
Louis: Beau Ances, John C. Morris, David Winkfield, Maria Carroll, Angela Oliver, Mary L.
Creech – Past Investigator, Mark A. Mintun – Past Investigator, Stacy Schneider – Past
Investigator. University of Alabama - Birmingham: Daniel Marson, David Geldmacher, Marissa
Natelson Love, Randall Griffith – Past Investigator, David Clark – Past Investigator, John
Brockington – Past Investigator. Mount Sinai School of Medicine: Hillel Grossman, Effie Mitsis –
Past Investigator. Rush University Medical Center: Raj C. Shah, Melissa Lamar, Patricia Samuels.
Wien Center: Ranjan Duara, Maria T. Greig-Custo, Rosemarie Rodriguez. Johns Hopkins
University: Marilyn Albert, Chiadi Onyike, Daniel D’Agostino II, Stephanie Kielb – Past
Investigator. New York University: Martin Sadowski, Mohammed O. Sheikh, Jamika Singleton-

15
Garvin, Anaztasia Ulysse, Mrunalini Gaikwad. Duke University Medical Center: P. Murali
Doraiswamy, Jeffrey R. Petrella, Olga James, Salvador Borges-Neto, Terence Z. Wong – Past
Investigator, Edward Coleman – Past Investigator. University of Pennsylvania: Jason H.
Karlawish, David A. Wolk, Sanjeev Vaishnavi, Christopher M. Clark – Past Investigator, Steven
E. Arnold – Past Investigator. University of Kentucky: Charles D. Smith, Greg Jicha, Peter Hardy,
Riham El Khouli, Elizabeth Oates, Gary Conrad. University of Pittsburgh: Oscar L. Lopez,
MaryAnn Oakley, Donna M. Simpson. University of Rochester Medical Center: Anton P.
Porsteinsson, Kim Martin, Nancy Kowalksi, Melanie Keltz, Bonnie S. Goldstein – Past
Investigator, Kelly M. Makino – Past Investigator, M. Saleem Ismail – Past Investigator, Connie
Brand – Past Investigator. University of California Irvine IMIND: Gaby Thai, Aimee Pierce,
Beatriz Yanez, Elizabeth Sosa, Megan Witbracht. University of Texas Southwestern Medical
School: Kyle Womack, Dana Mathews, Mary Quiceno. Emory University: Allan I. Levey, James
J. Lah, Janet S. Cellar. University of Kansas, Medical Center: Jeffrey M. Burns, Russell H.
Swerdlow, William M. Brooks. University of California, Los Angeles: Ellen Woo, Daniel H.S.
Silverman, Edmond Teng, Sarah Kremen, Liana Apostolova – Past Investigator, Kathleen Tingus
– Past Investigator, Po H. Lu – Past Investigator, George Bartzokis – Past Investigator. Mayo
Clinic, Jacksonville: Neill R Graff-Radford (London), Francine Parfitt, Kim Poki-Walker. Indiana
University: Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews – Past Investigator, Jared R.
Brosch, Scott Herring. Yale University School of Medicine: Christopher H. van Dyck, Richard E.
Carson, Pradeep Varma. McGill Univ., Montreal-Jewish General Hospital: Howard Chertkow,
Howard Bergman, Chris Hosein. Sunnybrook Health Sciences, Ontario: Sandra Black, Bojana
Stefanovic, Chris (Chinthaka) Heyn. U.B.C. Clinic for AD & Related Disorders: Ging-Yuek Robin
Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman – Past Investigator, Michele Assaly – Past
Investigator. Cognitive Neurology - St. Joseph's, Ontario: Elizabeth Finger, Stephen Pasternak,
William Pavlosky, Irina Rachinsky – Past Investigator, Dick Drost – Past Investigator, Andrew
Kertesz – Past Investigator. Cleveland Clinic Lou Ruvo Center for Brain Health: Charles Bernick,
Donna Muni. Northwestern University: Marek-Marsel Mesulam, Emily Rogalski, Kristine
Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin – Past Investigator, Chuang-
Kuo Wu,– Past Investigator, Nancy Johnson – Past Investigator. Premiere Research Inst (Palm
Beach Neurology): Carl Sadowsky, Teresa Villena. Georgetown University Medical Center:
Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds. Brigham and Women's Hospital:
Reisa A. Sperling, Keith A. Johnson, Gad A. Marshall. Stanford University: Jerome Yesavage,
Joy L. Taylor, Steven Chao, Barton Lane – Past Investigator, Allyson Rosen – Past Investigator,
Jared Tinklenberg – Past Investigator. Banner Sun Health Research Institute: Edward Zamrini,
Christine M. Belden, Sherye A. Sirrel. Boston University: Neil Kowall, Ronald Killiany, Andrew
E. Budson, Alexander Norbash – Past Investigator, Patricia Lynn Johnson – Past Investigator.
Howard University: Thomas O. Obisesan, Ntekim E. Oyonumo, Joanne Allard, Olu Ogunlana.
Case Western Reserve University: Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica.
University of California, Davis – Sacramento: Evan Fletcher, Pauline Maillard, John Olichney,
Charles DeCarli, Owen Carmichael – Past Investigator. Neurological Care of CNY: Smita Kittur
– Past Investigator. Parkwood Institute: Michael Borrie, T-Y Lee, Dr Rob Bartha. University of
Wisconsin: Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson. Banner Alzheimer's Institute:
Pierre Tariot, Anna Burke, Joel Hetelle, Kathryn DeMarco, Nadira Trncic – Past Investigator,
Adam Fleisher – Past Investigator, Stephanie Reeder – Past Investigator. Dent Neurologic
Institute: Vernice Bates, Horacio Capote, Michelle Rainka. Ohio State University: Douglas W.
Scharre, Maria Kataki, Rawan Tarawneh. Albany Medical College: Earl A. Zimmerman, Dzintra

16
Celmins, David Hart. Hartford Hospital, Olin Neuropsychiatry Research Center: Godfrey D.
Pearlson, Karen Blank, Karen Anderson. Dartmouth-Hitchcock Medical Center: Laura A.
Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli – Past Investigator. Wake Forest
University Health Sciences: Kaycee M. Sink, Mia Yang, Akiva Mintz. Rhode Island Hospital:
Brian R. Ott, Geoffrey Tremont, Lori A. Daiello. Butler Hospital: Courtney Bodge, Stephen
Salloway, Paul Malloy, Stephen Correia, Athena Lee. UC San Francisco: Howard J. Rosen, Bruce
L. Miller, David Perry. Medical University South Carolina: Jacobo Mintzer, Kenneth Spicer,
David Bachman. St. Joseph’s Health Care: Elizabeth Finger, Stephen Pasternak, Irina Rachinsky,
John Rogers, Andrew Kertesz – Past Investigator, Dick Drost – Past Investigator. Nathan Kline
Institute: Nunzio Pomara, Raymundo Hernando, Antero Sarrael. University of Iowa College of
Medicine: Delwyn D. Miller, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub
Shim, Susan K. Schultz – Past Investigator. Cornell University: Norman Relkin, Gloria Chiang,
Michael Lin, Lisa Ravdin. University of South Florida: USF Health Byrd Alzheimer’s Institute:
Amanda Smith, Christi Leach, Balebail Ashok Raj – Past Investigator, Kristin Fargher – Past
Investigator.

CHARGE Consortium
Edith Hofer (Clinical Division of Neurogeriatrics, Department of Neurology, Medical University
of Graz, Graz, Austria), Gennady V. Roshchupkin (Department of Radiology and Nuclear
Medicine, Erasmus MC, Rotterdam, The Netherlands), Hieab H. H. Adams (Department of
Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands), Maria J. Knol
(Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands), Honghuang Lin
(Section of Computational Biomedicine, Department of Medicine, Boston University School of
Medicine, Boston, MA, USA), Shuo Li (Department of Biostatistics, Boston University School of
Public Health, Boston, MA, USA), Habil Zare (Glenn Biggs Institute for Alzheimer’s and
Neurodegenerative Diseases, UT Health San Antonio, San Antonio, USA), Shahzad Ahmad
(Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands), Nicola J. Armstrong
(Mathematics and Statistics, Murdoch University, Perth, Australia), Claudia L. Satizabal
(Department of Epidemiology and Biostatistics, Glenn Biggs Institute for Alzheimer’s and
Neurodegenerative Diseases, UT Health San Antonio, San Antonio, USA), Manon Bernard
(Hospital for Sick Children, Toronto, Canada), Joshua C. Bis (Cardiovascular Health Research
Unit, Department of Medicine, University of Washington, Seattle, WA, USA), Nathan A. Gillespie
(Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University,
VA, USA), Michelle Luciano (Centre for Cognitive Epidemiology and Cognitive Ageing,
University of Edinburgh, Edinburgh, UK), Aniket Mishra (University of Bordeaux, Bordeaux
Population Health Research Center, INSERM UMR 1219, Bordeaux, France), Markus Scholz
(Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig,
Germany), Alexander Teumer (Institute for Community Medicine, University Medicine
Greifswald, Greifswald, Germany), Rui Xia (Institute of Molecular Medicine and Human Genetics
Center, University of Texas Health Science Center at Houston, Houston, TX, USA), Xueqiu Jian
(Institute of Molecular Medicine and Human Genetics Center, University of Texas Health Science
Center at Houston, Houston, TX, USA), Thomas H. Mosley (Department of Medicine, University
of Mississippi Medical Center, Jackson, MS, USA), Yasaman Saba (Gottfried Schatz Research
Center for Cell Signaling, Metabolism and Aging, Medical University of Graz, Graz, Austria),
Lukas Pirpamer (Clinical Division of Neurogeriatrics, Department of Neurology, Medical
University of Graz, Graz, Austria), Stephan Seiler (Imaging of Dementia and Aging (IDeA)

17
Laboratory, Department of Neurology, University of California-Davis, Davis, CA, USA), James
T. Becker (Departments of Psychiatry, Neurology, and Psychology, University of Pittsburgh,
Pittsburgh, PA, USA), Owen Carmichael (Pennington Biomedical Research Center, Baton Rouge,
LA, USA), Jerome I. Rotter (Institute for Translational Genomics and Population Sciences, Los
Angeles Biomedical Research Institute and Pediatrics at Harbor-UCLA Medical Center, Torrance,
CA, USA), Bruce M. Psaty (Cardiovascular Health Research Unit, Departments of Medicine,
Epidemiology and Health Services, University of Washington, Seattle, WA, USA), Oscar L. Lopez
(Departments of Psychiatry, Neurology, and Psychology, University of Pittsburgh, Pittsburgh, PA,
USA), Najaf Amin (Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands),
Mohsen Ghanbari (Department of Epidemiology, Erasmus MC, University Medical Center
Rotterdam, Rotterdam, The Netherlands), Sven J. van der Lee (Department of Epidemiology,
Erasmus MC, Rotterdam, The Netherlands), Qiong Yang (Department of Biostatistics, Boston
University School of Public Health, Boston, MA, USA), Jayandra J. Himali (Department of
Biostatistics, Boston University School of Public Health, Boston, MA, USA), Pauline Maillard
(Imaging of Dementia and Aging (IDeA) Laboratory, Department of Neurology, University of
California-Davis, Davis, CA, USA), Alexa S. Beiser (Department of Neurology, Boston
University School of Medicine, Boston, MA, USA), Charles DeCarli (Imaging of Dementia and
Aging (IDeA) Laboratory, Department of Neurology, University of California-Davis, Davis, CA,
USA), Sherif Karama (McGill University, Montreal Neurological Institute, Montreal, Canada),
Lindsay Lewis (McGill University, Montreal Neurological Institute, Montreal, Canada), Mat
Harris (Centre for Cognitive Epidemiology and Cognitive Ageing, University of Edinburgh,
Edinburgh, UK), Mark E. Bastin (Centre for Cognitive Epidemiology and Cognitive Ageing,
University of Edinburgh, Edinburgh, UK), Ian J. Deary (Centre for Cognitive Epidemiology and
Cognitive Ageing, University of Edinburgh, Edinburgh, UK), A. Veronica Witte (Department of
Neurology, Max Planck Institute of Cognitive and Brain Sciences, Leipzig, Germany), Frauke
Beyer (Department of Neurology, Max Planck Institute of Cognitive and Brain Sciences, Leipzig,
Germany), Markus Loeffler (Institute for Medical Informatics, Statistics and Epidemiology,
University of Leipzig, Leipzig, Germany), Karen A. Mather (Centre for Healthy Brain
Ageing,School of Psychiatry, University of New South Wales, Sydney, Australia), Peter R.
Schofield (Neuroscience Research Australia, Sydney, Australia), Anbupalam Thalamuthu (Centre
for Healthy Brain Ageing,School of Psychiatry, University of New South Wales, Sydney,
Australia), John B. Kwok (Brain and Mind Centre - The University of Sydney, Camperdown,
NSW, Australia), Margaret J. Wright (Queensland Brain Institute, The University of Queensland,
St Lucia, QLD, Australia), David Ames (National Ageing Research Institute, Royal Melbourne
Hospital, Victoria, Australia), Julian Trollor (Centre for Healthy Brain Ageing,School of
Psychiatry, University of New South Wales, Sydney, Australia), Jiyang Jiang (Centre for Healthy
Brain Ageing,School of Psychiatry, University of New South Wales, Sydney, Australia), Henry
Brodaty (Dementia Centre for Research Collaboration, University of New South Wales, Sydney,
NSW, Australia), Wei Wen (Centre for Healthy Brain Ageing,School of Psychiatry, University of
New South Wales, Sydney, Australia), Meike W. Vernooij (Department of Radiology and Nuclear
Medicine, Erasmus MC, Rotterdam, The Netherlands), Albert Hofman (Department of
Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA), André G.
Uitterlinden (Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands), Wiro J.
Niessen (Imaging Physics, Faculty of Applied Sciences, Delft University of Technology, The
Netherlands), Katharina Wittfeld (German Center for Neurodegenerative Diseases (DZNE), Site
Rostock/ Greifswald, Germany), Robin Bülow (Institute for Diagnostic Radiology and

18
Neuroradiology, University Medicine Greifswald, Greifswald, Germany), Uwe Völker
(Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald,
Greifswald, Germany), Zdenka Pausova (Hospital for Sick Children, Toronto, Canada), G. Bruce
Pike (Departments of Radiology and Clinial Neurosciences, University of Calgary, Calgary,
Canada), Sophie Maingault (University of Bordeaux, Institut des Maladies
NeurodégénrativesUMR5293, CEA, CNRS, Ubordeaux, Bordeaux, France), Fabrice Crivello
(University of Bordeaux, Institut des Maladies NeurodégénrativesUMR5293, CEA, CNRS,
Ubordeaux, Bordeaux, France), Christophe Tzourio (University of Bordeaux, Bordeaux
Population Health Research Center, INSERM UMR 1219, Bordeaux, France), Philippe Amouyel
(Centre Hospitalier Universitaire de Bordeaux, France; Inserm U1167, Lille, France), Bernard
Mazoyer (University of Bordeaux, Institut des Maladies NeurodégénrativesUMR5293, CEA,
CNRS, Ubordeaux, Bordeaux, France), Michael C. Neale (Virginia Institute for Psychiatric and
Behavior Genetics, Virginia Commonwealth University, VA, USA), Carol E. Franz (Department
of Psychiatry, University of California San Diego, CA, USA), Michael J. Lyons (Department of
Psychological and Brain Sciences, Boston University, Boston, MA, USA), Matthew S. Panizzon
(Department of Psychiatry, University of California San Diego, CA, USA), Ole A. Andreassen
(NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University
of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway),
Anders M. Dale (Departments of Radiology and Neurosciences, University of California, San
Diego, La Jolla, CA, USA), Mark Logue (National Center for PTSD at Boston VA Healthcare
System, Boston, MA, USA), Perminder S. Sachdev (Centre for Healthy Brain Ageing,School of
Psychiatry, University of New South Wales, Sydney, Australia), William S. Kremen (Department
of Psychiatry, University of California San Diego, CA, USA), Joanna M. Wardlaw (Centre for
Cognitive Epidemiology and Cognitive Ageing, University of Edinburgh, Edinburgh, UK), Arno
Villringer (Department of Neurology, Max Planck Institute of Cognitive and Brain Sciences,
Leipzig, Germany), Cornelia M. van Duijn (Department of Epidemiology, Erasmus MC,
Rotterdam, The Netherlands), Hans Jörgen Grabe (Department of Psychiatry and Psychotherapy,
University Medicine Greifswald, Germany), William T. Longstreth Jr (Departments of Neurology
and Epidemiology, University of Washington, Seattle, WA, USA), Myriam Fornage (Institute of
Molecular Medicine and Human Genetics Center, University of Texas Health Science Center at
Houston, Houston, TX, USA), Tomas Paus (Bloorview Research Institute, Holland Bloorview
Kids Rehabilitation Hospital, Toronto, Ontario, Canada), Stephanie Debette (University of
Bordeaux, Bordeaux Population Health Research Center, INSERM UMR 1219, Bordeaux,
France), M. Arfan Ikram (Department of Radiology and Nuclear Medicine, Erasmus MC,
Rotterdam, The Netherlands), Helena Schmidt (Gottfried Schatz Research Center for Cell
Signaling, Metabolism and Aging, Medical University of Graz, Graz, Austria), Reinhold Schmidt
(Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz,
Graz, Austria), Sudha Seshadri (Department of Epidemiology and Biostatistics, Glenn Biggs
Institute for Alzheimer’s and Neurodegenerative Diseases, UT Health San Antonio, San Antonio,
USA).

EPIGEN Consortium
David B. Goldstein (The Centre for Genomics and Population Genetics, Duke University Institute
for Genome Sciences and Policy, Durham, North Carolina, USA), Erin L. Heinzen (The Centre
for Genomics and Population Genetics, Duke University Institute for Genome Sciences and Policy,
Durham, North Carolina, USA), Kevin Shianna (The Centre for Genomics and Population

19
Genetics, Duke University Institute for Genome Sciences and Policy, Durham, North Carolina,
USA), Rodney Radtke (Department of Medicine, Duke University Medical Center, Durham, North
Carolina, USA) and Ruth Ottmann (Departments of Epidemiology, Neurology, and the G.H.
Sergievsky Center, Columbia University, New York, NY).

IMAGEN Consortium
Dr. Eric Artiges (INSERM), Semiha Aydin (Physikalisch-Technische Bundesanstalt), Prof. Dr.
Dr. Tobias Banaschewski (Central Institute of Mental Health), Alexis Barbot (Commissariat à
l'Energie Atomique), Prof. Dr. Gareth Barker (King's College London), Andreas Becker (Georg-
August-Universität Göttingen), Pauline Bezivin-Frere (INSERM), Dr. Francesca Biondo (King's
College London), Dr. Arun Bokde (Trinity College Dublin), Uli Bromberg (University of
Hamburg), Dr. Ruediger Bruehl, Prof. Dr. Christian Büchel (University of Hamburg), Dr.
Congying Chu (King's College London), Dr. Patricia Conrod (King's College London), Laura
Daedelow (Charité Universitätsmedizin Berlin), Dr. Jeffrey Dalley (Cambridge University), Dr.
Sylvane Desrivieres (King's College London), Eoin Dooley (Trinity College Dublin), Irina Filippi
(INSERM), Dr Ariane Fillmer (Physikalisch-Technische Bundesanstalt ), Prof. Dr. Herta Flor
(Central Institute of Mental Health), Juliane Fröhner (Technische Universität Dresden ), Vincent
Frouin (Commissariat à l'Energie Atomique), Dr. Hugh Garavan (University of Vermont), Prof.
Penny Gowland (University of Nottingham), Yvonne Grimmer (Central Institute of Mental
Health), Prof. Dr. Andreas Heinz (Charité Universitätsmedizin Berlin), Dr. Sarah Hohmann
(Central Institute of Mental Health), Albrecht Ihlenfeld (Physikalisch-Technische Bundesanstalt ),
Alex Ing (King's College London), Corinna Isensee (University Medical Center Göttingen ), Dr.
Bernd Ittermann (Physikalisch-Technische Bundesanstalt ), Dr. Tianye Jia (King's College
London), Dr. Hervé Lemaitre (INSERM), Emma Lethbridge (University of Nottingham), Prof. Dr.
Jean-Luc Martinot (INSERM), Sabina Millenet (Central Institute of Mental Health), Sarah Miller
(Charité Universitätsmedizin Berlin), Ruben Miranda (INSERM), PD Dr. Frauke Nees (Central
Institute of Mental Health), Dr. Marie-Laure Paillere (INSERM), Dimitri Papadopoulos
(INSERM), Prof. Dr. Tomáš Paus (Bloorview Research Institute, Holland Bloorview Kids
Rehabilitation Hospital and Departments of Psychology and Psychatry, University of Toronto),
Dr. Zdenka Pausova (University of Toronto), Dr. Dr. Jani Pentilla (INSERM), Dr. Jean-Baptiste
Poline (Commissariat à l'Energie Atomique), Prof. Dr. Luise Poustka (University Medical Center
Göttingen ), Dr. Erin Burke Quinlan (King's College London), Dr. Michael Rapp (Charité
Universitätsmedizin Berlin), Prof. Dr. Trevor Robbins (Cambridge University), Dr. Gabriel Robert
(King's College London), John Rogers (Delosis), Dr. Barbara Ruggeri (King's College London),
Prof. Dr. Gunter Schumann (King's College London), Prof. Dr. Michael Smolka (Technische
Universität Dresden), Argyris Stringaris (National Institute of Mental Health), Betteke van Noort
(Charité Universitätsmedizin Berlin), Dr. Henrik Walter (Charité Universitätsmedizin Berlin), Dr.
Robert Whelan (Trinity College Dublin), Prof. Dr. Steve Williams (King's College London).

Parkinson’s Progression Markers Initiative (PPMI)

Data used in preparing this article were obtained from the PPMI database (http://www.ppmi-
info.org/). As such, many investigators within the PPMI contributed to the design and
implementation of PPMI and/or provided data but did not participate in analysis or writing of this
report. A complete listing of PPMI investigators may be found at: http://www.ppmi-
info.org/authorslist/. Kenneth Marek (Institute for Neurodegenerative Disorders, New Haven),
Danna Jennings (Institute for Neurodegenerative Disorders, New Haven), Shirley Lasch (Institute

20
for Neurodegenerative Disorders, New Haven), Caroline Tanner (University of California, San
Francisco), Tanya Simuni (Northwestern University, Chicago), Christopher Coffey (University of
Iowa, Iowa City), Karl Kieburtz (Clinical Trials Coordination Center, University of Rochester),
Renee Wilson (Clinical Trials Coordination Center, University of Rochester), Werner Poewe
(Innsbruck Medical University, Innsbruck), Brit Mollenhauer (Paracelsus-Elena Klinik, Kassel),
Douglas Galasko (University of California, San Diego), Tatiana Foroud (Indiana University,
Indianapolis), Todd Sherer (The Michael J. Fox Foundation for Parkinson's Research, New York),
Sohini Chowdhury (The Michael J. Fox Foundation for Parkinson's Research, New York), Mark
Frasier (The Michael J. Fox Foundation for Parkinson's Research, New York), Catherine Kopil
(The Michael J. Fox Foundation for Parkinson's Research, New York), Vanessa Arnedo (The
Michael J. Fox Foundation for Parkinson's Research, New York), Alice Rudolph (Clinical Trials
Coordination Center, University of Rochester), Cynthia Casaceli (Clinical Trials Coordination
Center, University of Rochester), John Seibyl (Institute for Neurodegenerative Disorders, New
Haven), Susan Mendick (Institute for Neurodegenerative Disorders, New Haven), Norbert Schuff
(University of California, San Francisco), Chelsea Caspell (University of Iowa, Iowa City), Liz
Uribe (University of Iowa, Iowa City), Eric Foster (University of Iowa, Iowa City), Katherine
Gloer (University of Iowa, Iowa City), Jon Yankey (University of Iowa, Iowa City), Arthur Toga
(Laboratory of Neuroimaging (LONI), University of Southern California), Karen Crawford
(Laboratory of Neuroimaging (LONI), University of Southern California), Paola Casalin (BioRep,
Milan), Giulia Malferrari (BioRep, Milan), Andrew Singleton (National Institute on Aging, NIH,
Bethesda), Keith A. Hawkins (Yale University, New Haven), David Russell (Institute for
Neurodegenerative Disorders, New Haven), Stewart Factor (Emory University of Medicine,
Atlanta), Penelope Hogarth (Oregon Health and Science University, Portland), David Standaert
(University of Alabama at Birmingham, Birmingham), Robert Hauser (University of South
Florida, Tampa), Joseph Jankovic (Baylor College of Medicine, Houston), Matthew Stern
(University of Pennsylvania, Philadelphia), Lama Chahine (University of Pennsylvania,
Philadelphia), James Leverenz (University of Washington, Seattle), Samuel Frank (Boston
University, Boston), Irene Richard (University of Rochester, Rochester), Klaus Seppi (Innsbruck
Medical University, Innsbruck), Holly Shill (Banner Research Institute, Sun City), Hubert
Fernandez (Cleveland Clinic, Cleveland), Daniela Berg (University of Tuebingen, Tuebingen),
Isabel Wurster (University of Tuebingen, Tuebingen), Zoltan Mari (Johns Hopkins University,
Baltimore), David Brooks (Imperial College of London, London), Nicola Pavese (Imperial College
of London, London), Paolo Barone (University of Salerno, Salerno), Stuart Isaacson (Parkinson’s
Disease and Movement Disorders Center, Boca Raton), Alberto Espay (University of Cincinnati,
Cincinnati), Dominic Rowe (Macquarie University, Sydney), Melanie Brandabur (The Parkinson's
Institute, Sunnyvale), James Tetrud (The Parkinson's Institute, Sunnyvale), Grace Liang (The
Parkinson's Institute, Sunnyvale), Alex Iranzo (Hospital Clinic of Barcelona, Barcelona), Eduardo
Tolosa (Hospital Clinic of Barcelona, Barcelona), Shu-Ching Hu (University of Washington,
Seattle), Gretchen Todd (University of Washington, Seattle), Laura Leary (Institute for
Neurodegenerative Disorders, New Haven), Cheryl Riordan (Institute for Neurodegenerative
Disorders, New Haven), Linda Rees (The Parkinson's Institute, Sunnyvale), Alicia Portillo
(Oregon Health and Science University, Portland), Art Lenahan (Oregon Health and Science
University, Portland), Karen Williams (Northwestern University, Chicago), Stephanie Guthrie
(University of Alabama at Birmingham, Birmingham), Ashlee Rawlins (University of Alabama at
Birmingham, Birmingham), Sherry Harlan (University of South Florida, Tampa), Christine Hunter
(Baylor College of Medicine, Houston), Baochan Tran (University of Pennsylvania, Philadelphia),

21
Abigail Darin (University of Pennsylvania, Philadelphia), Carly Linder (University of
Pennsylvania, Philadelphia), Marne Baca (University of Washington, Seattle), Heli Venkov
(University of Washington, Seattle), Cathi-Ann Thomas (Boston University, Boston), Raymond
James (Boston University, Boston), Cheryl Deeley (University of Rochester, Rochester), Courtney
Bishop (University of Rochester, Rochester), Fabienne Sprenger (Innsbruck Medical University,
Innsbruck), Diana Willeke (Paracelsus-Elena Klinik, Kassel), Sanja Obradov (Banner Research
Institute, Sun City), Jennifer Mule (Cleveland Clinic, Cleveland), Nancy Monahan (Cleveland
Clinic, Cleveland), Katharina Gauss (University of Tuebingen, Tuebingen), Deborah Fontaine
(University of California, San Diego), Christina Gigliotti (University of California, San Diego),
Arita McCoy (Johns Hopkins University, Baltimore), Becky Dunlop (Johns Hopkins University,
Baltimore), Bina Shah (Imperial College of London, London), Susan Ainscough (University of
Salerno, Salerno), Angela James (Parkinson’s Disease and Movement Disorders Center, Boca
Raton), Rebecca Silverstein (Parkinson’s Disease and Movement Disorders Center, Boca Raton),
Kristy Espay (University of Cincinnati, Cincinnati), Madelaine Ranola (Macquarie University,
Sydney), Thomas Comery (Pfizer, Inc., Groton), Jesse Cedarbaum (Biogen Idec, Cambridge),
Bernard Ravina (Biogen Idec, Cambridge), Igor D. Grachev (GE Healthcare, Princeton), Jordan
S. Dubow (AbbVie, Abbot Park), Michael Ahlijanian (Bristol-Myers Squibb Company), Holly
Soares (Bristol-Myers Squibb Company), Suzanne Ostrowizki (F.Hoffmann La-Roche, Basel),
Paulo Fontoura (F.Hoffmann La-Roche, Basel), Alison Chalker (Merck & Co., North Wales),
David L. Hewitt (Merck & Co., North Wales), Marcel van der Brug (Genentech, Inc., South San
Francisco), Alastair D. Reith (GlaxoSmithKline, Stevenage), Peggy Taylor (Covance, Dedham),
Jan Egebjerg (H. Lundbeck), Mark Minton (Avid Radiopharmaceuticals, Philadelphia ), Andrew
Siderowf (Avid Radiopharmaceuticals, Philadelphia ), Pierandrea Muglia (UCB Pharma S.A.,
Brussels), Robert Umek (Meso Scale Discovery), Ana Catafau (Meso Scale Discovery), Vera
Kiyasova (Servier), Barbara Saba (Servier). SYS Consortium: Tomáš Paus MD PhD (Bloorview
Research Institute, University of Toronto, Canada), Zdenka Pausova, MD (The Hospital for Sick
Children, University of Toronto, Canada), G. Bruce Pike PhD (Department of Radiology,
University of Calgary, Canada), Louis Richer PhD (Department of Health Sciences, University of
Quebec in Chicoutimi, Canada), Gabriel Leonard PhD (Montreal Neurological Institute, McGill
University, Canada), Michel Perron PhD (CEGEP Jonquiere, Canada), Suzanne Veillette PhD
(CEGEP Jonquiere, Canada) and Manon Bernard BComp (The Hospital for Sick Children,
University of Toronto, Canada).

Enhancing NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA)-— Genetics

working group
Katrina L. Grasby, Neda Jahanshad, Jodie N. Painter, Lucía Colodro-Conde, Janita Bralten, Derrek
P. Hibar, Penelope A. Lind, Fabrizio Pizzagalli, Christopher R.K. Ching, Mary Agnes B.
McMahon, Natalia Shatokhina, Leo C.P. Zsembik, Ingrid Agartz, Saud Alhusaini, Marcio A.A.
Almeida, Dag Alnæs, Inge K. Amlien, Micael Andersson, Tyler Ard, Nicola J. Armstrong, Allison
Ashley-Koch, Joshua R. Atkins, Manon Bernard, Rachel M. Brouwer, Elizabeth E.L. Buimer,
Robin Bülow, Christian Bürger, Dara M. Cannon, Mallar Chakravarty, Qiang Chen, Joshua W.
Cheung, Baptiste Couvy-Duchesne, Anders M. Dale, Shareefa Dalvie, Tânia K. de Araujo, Greig
I. de Zubicaray, Sonja M.C. de Zwarte, Anouk den Braber, Nhat Trung Doan, Katharina Dohm,
Stefan Ehrlich, Hannah-Ruth Engelbrecht, Susanne Erk, Chun Chieh Fan, Iryna O. Fedko, Sonya
F. Foley, Judith M. Ford, Masaki Fukunaga, Melanie E. Garrett, Tian Ge, Sudheer Giddaluru,
Aaron L. Goldman, Melissa J. Green, Nynke A. Groenewold, Dominik Grotegerd, Tiril P. Gurholt,

22
Boris A. Gutman, Narelle K. Hansell, Mathew A. Harris, Marc B. Harrison, Courtney C. Haswell,
Michael Hauser, Stefan Herms, Dirk J. Heslenfeld, New Fei Ho, David Hoehn, Per Hoffmann,
Laurena Holleran, Martine Hoogman, Jouke-Jan Hottenga, Masashi Ikeda, Deborah Janowitz, Iris
E. Jansen, Tianye Jia, Christiane Jockwitz, Ryota Kanai, Sherif Karama, Dalia Kasperaviciute,
Tobias Kaufmann, Sinead Kelly, Masataka Kikuchi, Marieke Klein, Michael Knapp, Annchen R.
Knodt, Bernd Krämer, Max Lam, Thomas M. Lancaster, Phil H. Lee, Tristram A. Lett, Lindsay B.
Lewis, Iscia Lopes-Cendes, Michelle Luciano, Fabio Macciardi, Andre F. Marquand, Samuel R.
Mathias, Tracy R. Melzer, Yuri Milaneschi, Nazanin Mirza-Schreiber, Jose C.V. Moreira, Thomas
W. Mühleisen, Bertram Müller-Myhsok, Pablo Najt, Soichiro Nakahara, Kwangsik Nho, Loes M.
Olde Loohuis, Dimitri Papadopoulos Orfanos, John F. Pearson, Toni L. Pitcher, Benno Pütz, Yann
Quidé, Anjanibhargavi Ragothaman, Faisal M. Rashid, William R. Reay, Ronny Redlich, Céline
S. Reinbold, Jonathan Repple, Geneviève Richard, Brandalyn C. Riedel, Shannon L. Risacher,
Cristiane S. Rocha, Nina Roth Mota, Lauren Salminen, Arvin Saremi, Andrew J. Saykin, Fenja
Schlag, Lianne Schmaal, Peter R. Schofield, Rodrigo Secolin, Chin Yang Shapland, Li Shen, Jean
Shin, Elena Shumskaya, Ida E. Sønderby, Emma Sprooten, Lachlan T. Strike, Katherine E.
Tansey, Alexander Teumer, Anbupalam Thalamuthu, Sophia I. Thomopoulos, Diana Tordesillas-
Gutiérrez, Jessica A. Turner, Anne Uhlmann, Costanza Ludovica Vallerga, Dennis van der Meer,
Marjolein M.J. van Donkelaar, Liza van Eijk, Theo G.M. van Erp, Neeltje E.M. van Haren, Daan
van Rooij, Marie-José van Tol, Jan H. Veldink, Ellen Verhoef, Esther Walton, Mingyuan Wang,
Yunpeng Wang, Joanna M. Wardlaw, Wei Wen, Lars T. Westlye, Christopher D. Whelan,
Stephanie H. Witt, Katharina Wittfeld, Christiane Wolf, Thomas Wolfers, Jing Qin Wu, Clarissa
L. Yasuda, Dario Zaremba, Zuo Zhang, Alyssa H. Zhu, Marcel P. Zwiers, Eric Artiges, Amelia A.
Assareh, Rosa Ayesa-Arriola, Aysenil Belger, Christine L. Brandt, Gregory G. Brown, Sven
Cichon, Joanne E. Curran, Gareth E. Davies, Franziska Degenhardt, Michelle F. Dennis, Bruno
Dietsche, Srdjan Djurovic, Colin P. Doherty, Ryan Espiritu, Daniel Garijo, Yolanda Gil, Penny A.
Gowland, Robert C. Green, Alexander N. Häusler, Walter Heindel, Beng-Choon Ho, Wolfgang
U. Hoffmann, Florian Holsboer, Georg Homuth, Norbert Hosten, Clifford R. Jack Jr., MiHyun
Jang, Andreas Jansen, Nathan A. Kimbrel, Knut Kolskår, Sanne Koops, Axel Krug, Kelvin O.
Lim, Jurjen J. Luykx, Daniel H. Mathalon, Karen A. Mather, Venkata S. Mattay, Sarah Matthews,
Jaqueline Mayoral Van Son, Sarah C. McEwen, Ingrid Melle, Derek W. Morris, Bryon A. Mueller,
Matthias Nauck, Jan E. Nordvik, Markus M. Nöthen, Daniel S. O'Leary, Nils Opel, Marie-Laure
Paillère Martinot, G. Bruce Pike, Adrian Preda, Erin B. Quinlan, Paul E. Rasser, Varun Ratnakar,
Simone Reppermund, Vidar M. Steen, Paul A. Tooney, Fábio R. Torres, Dick J. Veltman, James
T. Voyvodic, Robert Whelan, Tonya White, Hidenaga Yamamori, Marina K.M. Alvim, David
Ames, Tim J. Anderson, Ole A. Andreassen, Alejandro Arias-Vasquez, Mark E. Bastin, Bernhard
T. Baune, Jean C. Beckham, John Blangero, Dorret I. Boomsma, Henry Brodaty, Han G. Brunner,
Randy L. Buckner, Jan K. Buitelaar, Juan R. Bustillo, Wiepke Cahn, Murray J. Cairns, Vince
Calhoun, Vaughan J. Carr, Xavier Caseras, Svenja Caspers, Gianpiero L. Cavalleri, Fernando
Cendes, Aiden Corvin, Benedicto Crespo-Facorro, John C. Dalrymple-Alford, Udo Dannlowski,
Eco J.C. de Geus, Ian J. Deary, Norman Delanty, Chantal Depondt, Sylvane Desrivières, Gary
Donohoe, Thomas Espeseth, Guillén Fernández, Simon E. Fisher, Herta Flor, Andreas J. Forstner,
Clyde Francks, Barbara Franke, David C. Glahn, Randy L. Gollub, Hans J. Grabe, Oliver Gruber,
Asta K. Håberg, Ahmad R. Hariri, Catharina A. Hartman, Ryota Hashimoto, Andreas Heinz, Frans
A. Henskens, Manon H.J. Hillegers, Pieter J. Hoekstra, Avram J. Holmes, L. Elliot Hong, Hilleke
E. Hulshoff Pol, Terry L. Jernigan, Erik G. Jönsson, René S. Kahn, Martin A. Kennedy, Tilo T.J.
Kircher, Peter Kochunov, John B.J. Kwok, Stephanie Le Hellard, Carmel M. Loughland, Nicholas

23
G. Martin, Jean-Luc Martinot, Colm McDonald, Katie L. McMahon, Andreas Meyer-Lindenberg,
Patricia T. Michie, Rajendra A. Morey, Bryan Mowry, Lars Nyberg, Jaap Oosterlaan, Roel A.
Ophoff, Christos Pantelis, Tomas Paus, Zdenka Pausova, Brenda W.J.H. Penninx, Tinca J.C.
Polderman, Danielle Posthuma, Marcella Rietschel, Joshua L. Roffman, Laura M. Rowland,
Perminder S. Sachdev, Philipp G. Sämann, Ulrich Schall, Gunter Schumann, Rodney J. Scott,
Kang Sim, Sanjay M. Sisodiya, Jordan W. Smoller, Iris E. Sommer, Beate St Pourcain, Dan J.
Stein, Arthur W. Toga, Julian N. Trollor, Nic J.A. Van der Wee, Dennis van 't Ent, Henry Völzke,
Henrik Walter, Bernd Weber, Daniel R. Weinberger, Margaret J. Wright, Juan Zhou, Jason L.
Stein, Paul M. Thompson, Sarah E. Medland.

Additional Cohort Information

1000BRAINS
Is a population-based cohort based on the Heinz-Nixdorf Recall Study (HNR) and is supported in
part by the German National Cohort. We thank the Heinz Nixdorf Foundation (Germany) for their
generous support in terms of the Heinz Nixdorf Study.

ADNI1 and ADNI2GO

Data used in the preparation of this article were obtained from the Alzheimer's Disease
Neuroimaging Initiative database (adni.loni.usc.edu). The ADNI was launched in 2003 as a 5-year
public–private partnership, led by Principal Investigator Michael W. Weiner, MD. The primary
goal of ADNI has been to test whether serial magnetic resonance imaging (MRI), positron
emission tomography (PET), other biological markers, and clinical and neuropsychological
assessment can be combined to measure the progression of mild cognitive impairment (MCI) and
early Alzheimer’s disease (AD) and to assess and optimize biomarkers for clinical trials in AD.
The initial sample included older adults who were cognitive normal (CN) as well as meeting
criteria for MCI and clinical AD. In 2011, ADNI-2 began to recruit an additional CN group as well
as individuals with significant memory concerns (SMC), early MCI and late MCI, and AD. These
subjects, and others carried forward from ADNI-1, were scanned with an updated neuroimaging
protocol. Participants were recruited from over 60 sites across the U.S. and Canada. For up-to-date
information, please see www.adni-info.org. ADNI data are disseminated by the Laboratory for
Neuro Imaging at the University of Southern California.

ALSPAC
Pregnant women resident in Avon, UK with expected dates of delivery 1st April 1991 to 31st
December 1992 were invited to take part in the study. The initial number of pregnancies enrolled
is 14,541 (for these at least one questionnaire has been returned or a “Children in Focus” clinic
had been attended by 19/07/99). Of these initial pregnancies, there was a total of 14,676 fetuses,
resulting in 14,062 live births and 13,988 children who were alive at 1 year of age. When the oldest
children were approximately 7 years of age, an attempt was made to bolster the initial sample with
eligible cases who had failed to join the study originally. As a result, when considering variables
collected from the age of seven onwards (and potentially abstracted from obstetric notes) there are
data available for more than the 14,541 pregnancies mentioned above. The number of new
pregnancies not in the initial sample (known as Phase I enrolment) that are currently represented
on the built files and reflecting enrolment status at the age of 18 is 706 (452 and 254 recruited
during Phases II and III respectively), resulting in an additional 713 children being enrolled. The

24
phases of enrolment are described in more detail in the cohort profile paper (see footnote 4 below).
The total sample size for analyses using any data collected after the age of seven is therefore 15,247
pregnancies, resulting in 15,458 fetuses. Of this total sample of 15,458 fetuses, 14,775 were live
births and 14,701 were alive at 1 year of age. A 10% sample of the ALSPAC cohort, known as the
Children in Focus (CiF) group, attended clinics at the University of Bristol at various time intervals
between 4 to 61 months of age. The CiF group were chosen at random from the last 6 months of
ALSPAC births (1432 families attended at least one clinic). Excluded were those mothers who had
moved out of the area or were lost to follow-up, and those partaking in another study of infant
development in Avon. The data used in the present study were collected from 391 males and
further description of this subset and the variables used in this study are provided in Tables S2–
S4. Ethical approval for the study was obtained from the ALSPAC Ethics and Law Committee and
the Local Research Ethics Committees. This publication is the work of the authors and they will
serve as guarantors for the contents of this paper. The study website contains details of all the data
that is available through a fully searchable data dictionary
(http://www.bris.ac.uk/alspac/researchers/data-access/data-dictionary/). Further information can
be found in the following papers: Boyd A, Golding J, Macleod J, Lawlor DA, Fraser A, Henderson
J, Molloy L, Ness A, Ring S, Davey Smith G. Cohort Profile: The ‘Children of the 90s’; the index
offspring of The Avon Longitudinal Study of Parents and Children (ALSPAC). International
Journal of Epidemiology 2013; 42: 111-127; Fraser A, Macdonald-Wallis C, Tilling K, Boyd A,
Golding J, Davey Smith G, Henderson J, Macleod J, Molloy L, Ness A, Ring S, Nelson SM,
Lawlor DA. Cohort Profile: The Avon Longitudinal Study of Parents and Children: ALSPAC
mothers cohort. International Journal of Epidemiology 2013; 42:97-110.

BIG
The Brain Imaging Genetics (BIG) database was established in Nijmegen, the Netherlands in 2007.
This resource is now part of Cognomics, a joint initiative by researchers of the Donders Centre for
Cognitive Neuroimaging, the Human Genetics and Cognitive Neuroscience departments of the
Radboud University Medical Center, and the Max Planck Institute for Psycholinguistics (funded
by the Max Planck Society). The present study includes two subsamples of BIG, from successive
waves of genotyping on Affymetrix (BIG-Affy) and PsychChip (BIG-PsychChip) arrays.
Analyses for this project were carried out on the Dutch national e-infrastructure with the support
of SURF Cooperative.

GIG
The GIG (Genomic Imaging Göttingen) sample was established at the Center for Translational
Research in Systems Neuroscience and Psychiatry (Head: Prof. Dr. O. Gruber) at Göttingen
University.

GSP: Brain Genomics Superstruct Project (GSP): Data were provided [in part] by the Brain GSP
of Harvard University and the Massachusetts General Hospital, with support from the Center for
BrainScience Neuroinformatics Research Group, the Athinoula A. Martinos Center for Biomedical
Imaging and the Center for Human Genetic Research. Twenty individual investigators at Harvard
and Massachusetts General Hospital generously contributed data to GSP.

HUNT

25
The HUNT Study is a collaboration between HUNT Research Centre (Faculty of Medicine and
Movement Sciences, NTNU – Norwegian University of Science and Technology), Nord-
Trøndelag County Council, Central Norway Health Authority, and the Norwegian Institute of
Public Health.

IMpACT
The International Multi-centre persistent ADHD CollaboraTion (IMpACT), is a consortium of
clinical and basic researchers from several European countries (The Netherlands, Germany, Spain,
Norway, The United Kingdom, Sweden), from the United States of America, and from Brazil.

LBC1936
The work was undertaken as part of the Cross Council and University of Edinburgh Centre for
Cognitive Ageing and Cognitive Epidemiology (CCACE; http://www.ccace.ed.ac.uk). The image
acquisition and analysis was performed at the Brain Research Imaging Centre, University of
Edinburgh (http://www.bric.ed.ac.uk).

MPIP
The MPIP Munich Morphometry Sample comprises images acquired as part of the Munich
Antidepressant Response Signature (MARS) Study and the Recurrent Unipolar Depression (RUD)
Case-Control study performed at the MPIP, and control subjects acquired at the Ludwig-
Maximilians-University, Munich, Department of Psychiatry. PPMI: Data used in the preparation
of this article were obtained from the Parkinson’s Progression Markers Initiative (PPMI) database
(www.ppmi-info.org/data). For up-to-date information on the study, visit www.ppmi-info.org.

UK Biobank
This research has been conducted using the UK Biobank Resource under Application Number
‘11559’.

Supplementary Acknowledgements
International Frontotemporal Dementia GWAS Consortium
Authors: Raffaele Ferrari, Dena G Hernandez, Michael A Nalls, Jonathan D Rohrer, Adaikalavan
Ramasamy, John BJ Kwok, Carol Dobson-Stone, William S Brooks, Peter R Schofield, Glenda M
Halliday, John R Hodges, Olivier Piguet, Lauren Bartley, Elizabeth Thompson, Eric Haan, Isabel
Hernández, Agustín Ruiz, Mercè Boada, Barbara Borroni, Alessandro Padovani, Carlos Cruchaga,
Nigel J Cairns, Luisa Benussi, Giuliano Binetti, Roberta Ghidoni, Gianluigi Forloni, Diego Albani,
Daniela Galimberti, Chiara Fenoglio, Maria Serpente, Elio Scarpini, Jordi Clarimón, Alberto Lleó,
Rafael Blesa, Maria Landqvist Waldö, Karin Nilsson, Christer Nilsson, Ian RA Mackenzie, Ging-
Yuek R Hsiung, David MA Mann, Jordan Grafman, Christopher M Morris, Johannes Attems, Ian
G McKeith, Alan J Thomas, Pietro Pietrini, Edward D Huey, Eric M Wassermann, Atik Baborie,
Evelyn Jaros, Michael C Tierney, Pau Pastor, Cristina Razquin, Sara Ortega-Cubero, Elena
Alonso, Robert Perneczky, Janine Diehl- Schmid, Panagiotis Alexopoulos, Alexander Kurz,
Innocenzo Rainero, Elisa Rubino, Lorenzo Pinessi, Ekaterina Rogaeva, Peter St George-Hyslop,
Giacomina Rossi, Fabrizio Tagliavini, Giorgio Giaccone, James B Rowe, Johannes CM
Schlachetzki, James Uphill, John Collinge, Simon Mead, Adrian Danek, Vivianna M Van Deerlin,
Murray Grossman, John Q Trojanowski, Julie van der Zee, Marc Cruts, Christine Van

26
Broeckhoven, Stefano F Cappa, Isabelle Leber, Didier Hannequin, Véronique Golfier, Martine
Vercelletto, Alexis Brice, Benedetta Nacmias, Sandro Sorbi, Silvia Bagnoli, Irene Piaceri, Jørgen
E Nielsen, Lena E Hjermind, Matthias Riemenschneider, Manuel Mayhaus, Bernd Ibach, Gilles
Gasparoni, Sabrina Pichler, Wei Gu, Martin N Rossor, Nick C Fox, Jason D Warren, Maria Grazia
Spillantini, Huw R Morris, Patrizia Rizzu, Peter Heutink, Julie S Snowden, Sara Rollinson, Anna
Richardson, Alexander Gerhard, Amalia C Bruni, Raffaele Maletta, Francesca Frangipane, Chiara
Cupidi, Livia Bernardi, Maria Anfossi, Maura Gallo, Maria Elena Conidi, Nicoletta Smirne, Rosa
Rademakers, Matt Baker, Dennis W Dickson, Neill R Graff-Radford, Ronald C Petersen, David
Knopman, Keith A Josephs, Bradley F Boeve, Joseph E Parisi, William W Seeley, Bruce L Miller,
Anna M Karydas, Howard Rosen, John C van Swieten, Elise GP Dopper, Harro Seelaar, Yolande
AL Pijnenburg, Philip Scheltens, Giancarlo Logroscino, Rosa Capozzo, Valeria Novelli, Annibale
A Puca, Massimo Franceschi, Alfredo Postiglione, Graziella Milan, Paolo Sorrentino, Mark
Kristiansen, Huei-Hsin Chiang, Caroline Graff, Florence Pasquier, Adeline Rollin, Vincent
Deramecourt, Thibaud Lebouvier, Dimitrios Kapogiannis, Luigi Ferrucci, Stuart Pickering-
Brown, Andrew B Singleton, John Hardy, Parastoo Momeni.

Acknowledgements: Intramural funding from the National Institute of Neurological Disorders

and Stroke (NINDS) and National Institute on Aging (NIA), the Wellcome/MRC Centre on
Parkinson’s disease, Alzheimer’s Research UK (ARUK, Grant ARUK-PG2012-18) and by the
office of the Dean of the School of Medicine, Department of Internal Medicine, at Texas Tech
University Health Sciences Center. We thank Mike Hubank and Kerra Pearce at the Genomic
core facility at the Institute of Child Health (ICH), University College of London (UCL), for
assisting RF in performing Illumina genotyping experiments (FTD-GWAS genotyping). This
study utilized the high-performance computational capabilities of the Biowulf Linux cluster at
the National Institutes of Health, Bethesda, Md. (http://biowulf.nih.gov). North American Brain
Expression Consortium (NABEC) - The work performed by the North American Brain
Expression Consortium (NABEC) was supported in part by the Intramural Research Program of
the National Institute on Aging, National Institutes of Health, part of the US Department of
Health and Human Services; project number ZIA AG000932-04. In addition this work was
supported by a Research Grant from the Department of Defense, W81XWH-09-2-0128. UK
Brain Expression Consortium (UKBEC) - This work performed by the UK Brain Expression
Consortium (UKBEC) was supported by the MRC through the MRC Sudden Death Brain Bank
(C.S.), by a Project Grant (G0901254 to J.H. and M.W.) and by a Fellowship award (G0802462
to M.R.). D.T. was supported by the King Faisal Specialist Hospital and Research Centre, Saudi
Arabia. Computing facilities used at King's College London were supported by the National
Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St
Thomas' NHS Foundation Trust and King's College London. We would like to thank AROS
Applied Biotechnology AS company laboratories and Affymetrix for their valuable input. RF’s
work is supported by Alzheimer’s Society (grant number 284), UK; JBJK was supported by the
National Health and Medical Resarch Council (NHMRC) Australia, Project Grants 510217 and
1005769; CDS was supported by NHMRC Project Grants 630428 and 1005769; PRS was
supported by NHMRC Project Grants 510217 and 1005769 and acknowledges that DNA
samples were prepared by Genetic Repositories Australia, supported by NHMRC Enabling Grant
401184; GMH was supported by NHMRC Research Fellowship 630434, Project Grant 1029538,
Program Grant 1037746; JRH was supported by the Australian Research Council Federation
Fellowship, NHMRC Project Grant 1029538, NHMRC Program Grant 1037746; OP was

27
supported by NHMRC Career Development Fellowship 1022684, Project Grant 1003139. IH,
AR and MB acknowledge the patients and controls who participated in this project and the
Trinitat Port-Carbó and her family who are supporting Fundació ACE research programs. CC
was supported by Grant P30- NS069329-01 and acknowledges that the recruitment and clinical
characterization of research participants at Washington University were supported by NIH P50
AG05681, P01 AG03991, and P01 AG026276. LB and GB were supported by the Ricerca
Corrente, Italian Ministry of Health; RG was supported by Fondazione CARIPLO 2009-2633,
Ricerca Corrente, Italian Ministry of Health; GF was supported by Fondazione CARIPLO 2009-
2633. ES was supported by the Italian Ministry of Health; CF was supported by Fondazione
Cariplo; MS was supported from the Italian Ministry of Health (Ricerca Corrente); MLW was
supported by Government funding of clinical research within NHS Sweden (ALF); KN was
supported by Thure Carlsson Foundation; CN was supported by Swedish Alzheimer Fund.
IRAM and GYRH were supported by CIHR (grant 74580) PARF (grant C06-01). JG was
supported by the NINDS intramural research funds for FTD research. CMM was supported by
Medical Research Council UK, Brains for Dementia Research, Alzheimer's Society, Alzheimer's
Research UK, National Institutes for Health Research, Department of Health, Yvonne Mairy
Bequest and acknowledges that tissue made available for this study was provided by the
Newcastle Brain Tissue Resource, which was funded in part by grants G0400074 and G1100540
from the UK MRC, the Alzheimer’s Research Trust and Alzheimer’s Society through the Brains
for Dementia Research Initiative and an NIHR Biomedical Research Centre Grant in Ageing and
Health, and NIHR Biomedical Research Unit in Lewy Body Disorders. CMM was supported by
the UK Department of Health and Medical Research Council and the Research was supported by
the National Institute for Health Research Newcastle Biomedical Research Centre based at
Newcastle Hospitals Foundation Trust and Newcastle University and acknowledges that the
views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the
Department of Health; JA was supported by MRC, Dunhill Medical Trust, Alzheimer's Research
UK; TDG was supported by Wellcome Trust Senior Clinical Fellow; IGM was supported by
NIHR Biomedical Research Centre and Unit on Ageing Grants and acknowledges the National
Institute for Health Research Newcastle Biomedical Research Centre based at Newcastle
Hospitals Foundation Trust and Newcastle University. The views expressed are those of the
author(s) and not necessarily those of the NHS, the NIHR or the Department of Health; AJT was
supported by Medical Research Council, Alzheimer's Society, Alzheimer's Research UK,
National Institutes for Health Research. EJ was supported by NIHR, Newcastle Biomedical
Research Centre. PP, CR, SOC and EA were supported partially by FIMA (Foundation for
Applied Medical Research); PP acknowledges Manuel Seijo-Martínez (Department of
Neurology, Hospital do Salnés, Pontevedra, Spain), Ramon Rene, Jordi Gascon and Jaume
Campdelacreu (Department of Neurology, Hospital de Bellvitge, Barcelona, Spain) for providing
FTD DNA samples. RP, JDS, PA and AK were supported by German Federal Ministry of
Education and Research (BMBF; grant number FKZ 01GI1007A – German FTLD consortium).
IR was supported by Ministero dell'Istruzione, dell'Università e della Ricerca (MIUR) of Italy.
PStGH was supported by the Canadian Institutes of Health Research, Wellcome Trust, Ontario
Research Fund. FT was supported by the Italian Ministry of Health (ricerca corrente) and MIUR
grant RBAP11FRE9; GR and GG were supported by the Italian Ministry of Health (ricerca
corrente). JBR was supported by Camrbidge NIHR Biomedical Research Centre and Wellcome
Trust (088324). JU, JC, SM were supported by the MRC Prion Unit core funding and
acknowledge MRC UK, UCLH Biomedical Research Centre, Queen Square Dementia BRU; SM

28
acknowledges the work of John Beck, Tracy Campbell, Gary Adamson, Ron Druyeh, Jessica
Lowe, Mark Poulter. AD acknowledges the work of Benedikt Bader and of Manuela Neumann,
Sigrun Roeber, Thomas Arzberger and Hans Kretzschmar†; VMVD and JQT were supported by
Grants AG032953, AG017586 and AG010124; MG was supported by Grants AG032953,
AG017586, AG010124 and NS044266; VMVD acknowledges EunRan Suh, PhD for assistance
with sample handling and Elisabeth McCarty-Wood for help in selection of cases; JQT
acknowledges Terry Schuck, John Robinson and Kevin Raible for assistance with
neuropathological evaluation of cases. CVB and the Antwerp site were in part funded by the
MetLife Foundation for Medical Research Award (to CVB), the Belgian Science Policy Office
(BELSPO) Interuniversity Attraction Poles program; the Alzheimer Research Foundation (SAO-
FRA); the Medical Foundation Queen Elisabeth (GSKE); the Flemish Government initiated
Methusalem Excellence Program (to CVB); the Research Foundation Flanders (FWO) and the
University of Antwerp Research Fund. CVB, MC and JvdZ acknowledge the neurologists S
Engelborghs, PP De Deyn, A Sieben, R Vandenberghe and the neuropathologist JJ Martin for the
clinical and pathological diagnoses. CVB, MC and JvdZ further thank the personnel of the
Genetic Service Facility of the VIB Department of Molecular Genetics
(http://www.vibgeneticservicefacility.be) and the Antwerp Biobank of the Institute Born-Bunge
for their expert support. IL and AB were supported by the program “Investissements d’avenir”
ANR-10-IAIHU-06 and acknowledges the contribution of The French research network on
FTLD/FTLD-ALS for the contribution in samples collection. BN is founded by Fondazione
Cassa di Risparmio di Pistoia e Pescia (grant 2014.0365), SS is founded by the Cassa di
Risparmio di Firenze (grant 2014.0310) and a grant from Ministry of Health n° RF-2010-
2319722. JEN was supported by the Novo Nordisk Foundation, Denmark. MR was supported by
the German National Genome Network (NGFN); German Ministry for Education and Research
Grant Number 01GS0465. JDR, MNR, NCF and JDW were supported by an MRC programme
grant and the Dementia Platform UK, the NIHR Queen Square Dementia Biomedical Research
Unit (BRU) and the Leonard Wolfson Experimental Neurology Centre. MGS was supported by
MRC grant n G0301152, Cambridge Biomedical Research Centre and acknowledges Mrs K
Westmore for extracting DNA. HM was supported by the Motor Neuron Disease Association
(Grant 6057). RR was supported by P50 AG016574, R01 NS080882, R01 NS065782, P50
NS72187 and the Consortium for Frontotemporal Dementia; DWD was supported by
P50NS072187, P50AG016574, State of Florida Alzheimer Disease Initiative, & CurePSP, Inc.;
NRGR, JEP, RCP, DK, BFB were supported by P50 AG016574; KAJ was supported by R01
AG037491; WWS was supported by NIH AG023501, AG019724, Consortium for
Frontotemporal Dementia Research; BLM was supported by P50AG023501, P01AG019724,
Consortium for FTD Research; HR was supported by AG032306. JCvS was supported by
Stichting Dioraphte Foundation (11 02 03 00), Nuts Ohra Foundation (0801-69), Hersenstichting
Nederland (BG 2010-02) and Alzheimer Nederland. CG and HHC acknowledge families,
patients, clinicians including Dr Inger Nennesmo and Dr Vesna Jelic, Professor Laura Fratiglioni
for control samples and Jenny Björkström, Håkan Thonberg, Charlotte Forsell, Anna-Karin
Lindström and Lena Lilius for sample handling. CG was supported by Swedish Brain Power
(SBP), the Strategic Research Programme in Neuroscience at Karolinska Institutet (StratNeuro),
the regional agreement on medical training and clinical research (ALF) between Stockholm
County Council and Karolinska Institutet, Swedish Alzheimer Foundation, Swedish Research
Council, Karolinska Institutet PhD-student funding, King Gustaf V and Queen Victoria’s Free
Mason Foundation. FP, AR, VD and FL acknowledge Labex DISTALZ. RF acknowledges the

29
help and support of Mrs. June Howard at the Texas Tech University Health Sciences Center
Office of Sponsored Programs for tremendous help in managing Material Transfer Agreement at
TTUHSC.

30
 European participants Non-European

Principal Replication Generalization

23,909 2,943
10,083 14,727
participants from participants from
participants from participants from
49 ENIGMA 8 ENIGMA
UK Biobank 1 ENIGMA cohort + CHARGE
cohorts cohorts

369 GWS loci

244 SNPs
25 INDELs

360 loci
available in 307 GWS loci
replication data

292 loci 285 GWS loci

available in 279 loci same direction as
generalization data Europeans
238 loci beta within 95% CIs of
Europeans
136 loci became more significant

Fig. S1.
Flow chart summarizing the phases of meta-analysis. GWS: genome-wide significant.

31
Fig. S2. (see external file ManhattanPlots.pdf)
Manhattan plots of each trait from the principal meta-analysis.

32
Fig. S3. (see external fileQQPlots.pdf)
QQ plots of each region from the principal meta-analysis.

33
Fig. S4. (see external file Forest Plots.pdf).
Forest plots of the 369 genome-wide significant loci

34
Fig. S5. (see external file LocusZoom.pdf).
LocusZoom plots of the 369 genome-wide significant loci

35
Fig. S6.
Partitioned heritability enrichment analyses (A) active regulatory elements across tissues and cell
types, (B) temporally specific active regulatory elements, (C) regulatory elements of cell-type
specific genes in fetal brain, and (D) differentially accessible regions between progenitor-
enriched germinal zone (GZ) and neuron-enriched cortical plate (CP).

36
Fig. S7.
Significance of the enrichment of gene ontology annotations for (A) total surface area, and (B)
multivariate regional surface area from TATES output.

37
Fig. S8.
Regional association plot for the 3p24.1 locus (rs12630663). Localizing EOMES, validated
enhancer regulating EOMES expression, chromatin interaction, and microcephaly associated
translocation breakpoint.

38
Fig. S9.
Clustering of genetic correlations among (A) surface area and (B) thickness regions after
correcting for global measures. Clustering of genetic correlations among (C) surface area and (D)
thickness regions without correcting for global measures. The best-fitting model for surface area
and thickness with global correction was 4 diagonal components with varying volume and shape.
The best-fitting model for surface area and thickness without global correction was 5 spherical
components with varying volume.

39
Fig. S10.
P-value of genome-wide significant regional SNPs with global control compared to their P-value
in the global measure for (A) surface area and (B) thickness. Effect size of genome-wide
significant regional SNPs with global control compared to their effect size in global measures for
(C) surface area and (D) thickness. Effect size of genome-wide significant regional SNPs with
global control compared to regional SNPs without global control in (E) surface area and (F)
thickness.
40
Fig. S11. (see external file PhenotypicPlots.pdf)
Phenotypic distribution plots from each cohort and trait included in the meta-analyses.

41
Tables S1 to S20 (separate file Grasby_etal_Supplementary_Tables.xlsx).
Table S1.
Phenotype descriptions

Table S2.
Cohort descriptions

Table S3.
Description of the imaging data for each cohort and percentage of individuals retained in each
cohort after quality control who were taken forward to the GWAS analyses for each cohort and
each trait

Table S4.
Description of the genotype data for each cohort

Table S5.
Meta-analytic GWAS results for the 369 loci taken forward for replication

Table S6.
Results from MAGMA gene based tests

Table S7.
Univariate heritability (twin and SNP) for global and regional surface area and thickness

Table S8.
Polygenic risk score results for global and regional surface area and thickness

Table S9.
Genetic correlations (LD score rG) calculated between global cortical measures and selected
morphological traits

Table S10.
Results from DEPICT pathway based tests

Table S11.
Summary of bioinformatic functional follow-ups

Table S12.
eQTL and chromatin interaction information for lead SNPs and proxies

Table S13.
Results from CAVIAR fine-mapping

Table S14.
Genetic correlations (LD score rG) calculated from the GWAS of regional measures corrected for
global measures

42
Table S15.
Genetic correlations (LD score rG) calculated from the GWAS of regional measures not corrected
for global measures

Table S16.
Genetic correlations (LD score rG) calculated between the imaging phenotypes and selected
neuropsychiatric disorders and psychological traits

Table S17.
Genetic correlations (LD score rG) calculated between the imaging phenotypes and selected
neuropsychiatric disorders and psychological traits on healthy-only participants

Table S18.
Mendelian randomization analysis results for total SA and 8 correlated neuropsychological traits

Table S19.
Latent causal variable analysis results for total SA against 8 genetically correlated traits

Table S20.
Data access statements

43
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