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Genome-wide association study of positive emotion identifies a genetic variant and a role for microRNAs

Molecular Psychiatry volume 22, pages 774–783 (2017)Cite this article

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Abstract

Positive affect denotes a state of pleasurable engagement with the environment eliciting positive emotion such as contentment, enthusiasm or happiness. Positive affect is associated with favorable psychological, physical and economic outcomes in many longitudinal studies. With a heritability of ⩽64%, positive affect is substantially influenced by genetic factors; however, our understanding of genetic pathways underlying individual differences in positive affect is still limited. Here, through a genome-wide association study of positive affect in African-American participants, we identify a single-nucleotide polymorphism, rs322931, significantly associated with positive affect at P<5 × 10−8, and replicate this association in another cohort. Furthermore, we show that the minor allele of rs322931 predicts expression of microRNAs miR-181a and miR-181b in human brain and blood, greater nucleus accumbens reactivity to positive emotional stimuli and enhanced fear inhibition. Prior studies have suggested that miR-181a is part of the reward neurocircuitry. Taken together, we identify a novel genetic variant for further elucidation of genetic underpinning of positive affect that mediates positive emotionality potentially via the nucleus accumbens and miR-181.

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Acknowledgements

We appreciate the technical support of all of the staff and volunteers of the Grady Trauma Project, particularly Kimberly Kerley, Jordan Laird, Allen W Graham, Angelo Brown and Rebecca Roffman. We thank CF Gillespie, A Schwartz and T Weiss for medical support, A Lott for maintaining the database and Biao Zeng and Jing Zhao for genetic analytical support. We thank the participants of the Grady Trauma Project for their time and effort. We gratefully acknowledge the support of the Center for Health Discovery and Well Being and the Atlanta Clinical and Translational Science Institute for the clinical profiling of the CHDWB and the Georgia Tech Research Institute for start-up support to GG for genomic profiling. This study was supported in part by the Department of Veterans Affairs Career Development Award IK2CX000601 and the NARSAD Young Investigator Award (to APW). This work was primarily supported by the National Institutes of Mental Health (MH096764 and MH071537 to KJR; F32-MH101976 to JSS). Support was also received from Emory and Grady Memorial Hospital General Clinical Research Center, National Institutes of Health (NIH). TSW was supported by the Veterans Health Administration (BX001820) and NIH/NIA AG025688. The contents do not represent the views of the Department of Veterans Affairs or the United States Government.

Author contributions

All authors edited and commented on the manuscript. KJR obtained funding for the GWAS of positive affect, oversaw the GTP study and revised the manuscript. APW, LMA and JSS wrote the first draft of the manuscript. APW and LMA performed the GWAS of positive affect. APW performed the eQTL analyses in brain and blood. JSS designed the fMRI study and analyzed the fMRI data. GG provided the genetic data for the CHDWB cohort. GG and APW performed the genetic replication study. TJ designed the study of fear conditioning and analyzed the neurophysiology data. APW and TSW performed the GCTA heritability analysis. GT contributed to the miRNA data analysis. YL and PJ contributed to the generation of miRNA data. EBB contributed to the generation of GWAS data. BB contributed to the generation of positive affect data.

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Author notes

  1. A P Wingo, L M Almli and J S Stevens: These three authors contributed equally to this work.

Authors and Affiliations

  1. Atlanta Veterans Affairs Medical Center, Atlanta, GA, USA

    A P Wingo, T S Wingo, M Briscione & B Bradley

  2. Department of Psychiatry, School of Medicine, Emory University, Atlanta, GA, USA

    A P Wingo, L M Almli, J S Stevens, T Jovanovic, A Lori, M Briscione, B Bradley & K J Ressler

  3. Department of Neurology, School of Medicine, Emory University, Atlanta, GA, USA

    T S Wingo

  4. Department of Human Genetics, School of Medicine, Emory University, Atlanta, GA, USA

    T S Wingo, Y Li & P Jin

  5. Yerkes Research Center, Emory University, Atlanta, GA, USA

    G Tharp

  6. Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany

    E B Binder

  7. Center for Integrative Genomics, School of Biology, Georgia Institute of Technology, Atlanta, GA, USA

    G Gibson

  8. McLean Hospital, Harvard Medical School, Belmont, MA, USA

    K J Ressler

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  1. A P Wingo
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Correspondence to K J Ressler.

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Wingo, A., Almli, L., Stevens, J. et al. Genome-wide association study of positive emotion identifies a genetic variant and a role for microRNAs. Mol Psychiatry 22, 774–783 (2017). https://doi.org/10.1038/mp.2016.143

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