Alcoholism: Clinical and Experimental Research, Sep 1, 2022
BackgroundWe sought to clarify the impact of adolescent alcohol misuse on adult physical health a... more BackgroundWe sought to clarify the impact of adolescent alcohol misuse on adult physical health and subjective well‐being. To do so, we investigated both the direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction and the indirect effects on these outcomes attributable to subsequent alcohol problems.MethodThe sample included 2733 twin pairs (32% monozygotic; 52% female) from the FinnTwin16 study. Adolescent alcohol misuse was a composite of frequency of drunkenness, frequency of alcohol use, and alcohol problems at ages 16, 17, and 18.5. The early midlife outcomes included somatic symptoms, self‐rated health, and life satisfaction at age 34. The mediators examined as part of the indirect effect analyses included alcohol problems from the Rutgers Alcohol Problem Index at ages 24 and 34. Serial mediation and co‐twin comparison models were applied and included covariates from adolescence and early midlife.ResultsThere were weak direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction. However, there was stronger evidence for indirect effects, whereby young adult and early midlife alcohol problems serially mediated the relationship between adolescent alcohol misuse and early midlife somatic symptoms (β = 0.03, 95% CI [0.03, 0.04]), self‐rated health (β = −0.02, 95% CI [−0.03, −0.01]), and life satisfaction (β = −0.03, CI [−0.04, −0.02]). These serial mediation effects were robust in co‐twin comparison analyses.ConclusionsThese results provide evidence that alcohol problems are a primary driver linking adolescent alcohol misuse and poor health outcomes across the lifespan.
Aims To assess associations of intoxication frequency and number of drinks needed to become intox... more Aims To assess associations of intoxication frequency and number of drinks needed to become intoxicated in mid-adolescence with onset of psychiatric disorders in early adulthood. Design Prospective cohort study. Setting Northern Finland. Participants People from the Northern Finland Birth Cohort 1986 who self-reported adolescent alcohol use: 6,548 subjects (69.4% of the original sample). Data on alcohol use were collected using questionnaires at ages 15-16 years. Measurements Outcomes were any non-organic psychosis, mood disorder, anxiety disorder, any substance use disorder (SUD) and all the studied psychiatric disorders in early adulthood gathered from nationwide health care, pension and insurance registers. Number of drinks needed to become intoxicated was categorized into three classes: (1) No alcohol use or intoxication, and (2) low and (3) high alcohol tolerance (more than 7/9 drinks for females/males) groups. Similarly, intoxication frequency was divided into three classes: (1) never, (2) 1-2 times and (3) 3 or more times during the past 30 days. Information regarding gender, family type, other drug use, psychopathology using Youth Self-Report (YSR) total score, and parental psychiatric disorders were used as covariates. Findings In the multivariable analyses, both low [OR 3.0, 95% CI 1.3-6.7, p-value=0.009] and high [OR 4.4, 95% CI 1.8-11.1, p-value=0.001] alcohol tolerance were associated with increased risk of SUD. More frequent intoxication was associated with increased frequency of SUD [OR 3.9, 95% CI 2.0-7.3, p-value<0.
Alcoholism: Clinical and Experimental Research, Apr 4, 2011
Background-Long-term functional brain effects of adolescent alcohol abuse remain uncertain, parti... more Background-Long-term functional brain effects of adolescent alcohol abuse remain uncertain, partially because of difficulties in distinguishing inherited deficits from neuronal effects of ethanol and by confounds associated with alcohol abuse, especially nicotine exposure. We conducted a longitudinal twin study to determine neurocognitive effects of adolescent alcohol abuse, as measured with the auditory event-related potential (ERP) component P3, a putative marker of genetic vulnerability to alcoholism. Methods-Twin pairs (N = 177; 150 selected for intrapair concordance/ discordance for alcoholrelated problems at age 18½) were recruited from ongoing studies of twins born 1975-1979 in Finland. Alcohol and tobacco use were assessed with questionnaires at ages 16, 17, 18½, and ∼25, and by a structured psychiatric interview concurrent with the ERP testing at mean age 25.8. During ERP recordings, subjects were instructed to detect target tones within a train of frequent "standards" and to ignore occasional "novel" sounds. To distinguish familial factors from ethanol effects, ERP and self-reported alcohol use measures were incorporated into hierarchical multiple regression (HMR) analysis, and intrapair differences in ERP were associated with intrapair differences in alcohol variables. Results-Novel-sound P3 amplitude correlated negatively with self-reported alcohol use in both between-and within-family analyses. No similar effect was observed for target-tone P3. HMR results suggest that twins' similarity for novel-sound P3 amplitude is modulated by their alcohol use, and this effect of alcohol use is influenced by genetic factors. Conclusions-Our results, from a large sample of twins selected from a population-based registry for pairwise concordance/discordance for alcohol problems at 18½, demonstrate that adolescent alcohol abuse is associated with subtle neurophysiological changes in attention and orienting. The changes are reflected in decreased novel-sound P3 amplitude and may be modified by genetic factors.
This is a self-archived version of an original article. This version may differ from the original... more This is a self-archived version of an original article. This version may differ from the original in pagination and typographic details.
The factor mixture model (FMM) uses a hybrid of both categorical and continuous latent variables.... more The factor mixture model (FMM) uses a hybrid of both categorical and continuous latent variables. The FMM is a good model for the underlying structure of psychopathology because the use of both categorical and continuous latent variables allows the structure to be simultaneously categorical and dimensional. This is useful because both diagnostic class membership and the range of severity within and across diagnostic classes can be modeled concurrently. While the conceptualization of the FMM has been explained in the literature, the use of the FMM is still not prevalent. One reason is that there is little research about how such models should be applied in practice and, once a well fitting model is obtained, how it should be interpreted. In this paper, the FMM will be explored by studying a real data example on conduct disorder. By exploring this example, this paper aims to explain the different formulations of the FMM, the various steps in building a FMM, as well as how to decide between a FMM and alternative models. In recent years there has been a debate in the psychological literature about whether the underlying structure of psychological disorders, such as conduct disorder, is categorical or dimensional. In the categorical view, psychological disorders are represented by diagnostic categories that indicate whether a person is affected or unaffected by a disorder and/or whether a person has a specific subtype. This has been the predominant view of psychopathology because it has the advantage of meeting clinical needs and the needs of reporting for health care planners and insurance companies (Muthén, 2006). Alternatively, psychological disorders are considered dimensional in nature and are represented as a continuous distribution, with each individual having some amount of the disorder. The advantage of the dimensional view is that each disorder can be represented as a quantitative
Background-In 1990, Blum and colleagues first reported an association between DRD2 and alcoholism... more Background-In 1990, Blum and colleagues first reported an association between DRD2 and alcoholism. While there have been subsequent replications of this genetic association, there have also been numerous studies that failed to detect an association between DRD2 and alcohol dependence. We propose that one aspect contributing to this inconsistency is the variation in alcohol phenotype used across studies. Methods-Within the population based Finnish twin sample, FinnTwin16, we previously performed multivariate twin analyses to extract latent genetic factors which account for the variation across seven measures of alcohol consumption (frequency of drinking, frequency × quantity, frequency of heavy drinking, frequency of intoxication, and maximum drinks in a 24 hour period) and problems (the Rutgers Alcohol Problem Index-RAPI and the Mälmö-modified Michigan Alcohol Screen Test-MmMAST) in 3,065 twins. In the present study, we examined the association between thirty-one DRD2/ANKK1 SNPs and the genetic factor scores generated by twin analyses in a subset of FinnTwin16 (n=602). We focus on two of the genetic factors: a general alcohol consumption and problems factor score which represents shared genetic variance across alcohol measures, and an alcohol problems genetic factor score which loads onto the two indices of problematic drinking (MAST and RAPI). Results-After correction for multiple testing across SNPs and phenotypes, of the thirty-one SNPs genotyped across DRD2/ANKK1, one SNP (rs10891549) showed significant association with the general alcohol consumption and problems factor score (p=0.004), and four SNPs (rs10891549, rs1554929, rs6275, rs6279), representing 2 independent signals after accounting for LD, showed significant association with the alcohol problems genetic factor score (p=0.005, p=0.005, p=0.003, p=0.003). Conclusions-In this study, we provide additional positive evidence for the association between DRD2/ANKK1 and alcohol outcomes, including frequency of drinking and drinking problems. Additionally, post hoc analyses indicate stronger association signals using genetic factor scores than individual measures, which suggests that accounting for the genetic architecture of the alcohol measures reduces genetic heterogeneity in alcohol dependence outcomes in this sample and enhances the ability to detect association.
Robust sex differences in some spatial abilities that favor males have raised the question of whe... more Robust sex differences in some spatial abilities that favor males have raised the question of whether testosterone contributes to those differences. There is some evidence for prenatal organizational effects of testosterone on male-favoring spatial abilities, but not much is known about the role of pubertal testosterone levels on adult cognitive abilities. We studied the association between pubertal testosterone (at age 14) and cognitive performance in young adulthood (at age 21-23), assessing male-favoring, female-favoring, and sex-neutral cognitive domains in a population-based sample of 130 male and 178 female twins. Pubertal testosterone was negatively associated with performance in the Mental Rotation Test in young adult men (r = −.27), while among women no significant associations between testosterone and cognitive measures were detected. The significant association among men remained after controlling for pubertal development. Confirmatory within-family comparisons with one-sided significance testing yielded a negative correlation between twin pair differences in testosterone levels and Mental Rotation Test performances in 35 male twin pairs (r = −.32):the twin brother with higher testosterone performed less well on the Mental Rotation Test. That association was evident in18 pairs of dizygotic male twin pairs (r = −.42; analysis controlling for shared environmental effects). In contrast, the association of differences was not evident among 17 monozygotic male twin pairs (r = −.07; analysis controlling for shared genetic influences). Results suggest that pubertal testosterone levels are related specifically to male-favoring spatial ability and only among men. Within-family analyses implicated possible shared genetic effects between pubertal testosterone and mental rotation ability.
Scandinavian Journal of Medicine & Science in Sports, Jan 20, 2017
Because sustained physical activity is important for a healthy life, this paper examined whether ... more Because sustained physical activity is important for a healthy life, this paper examined whether a greater diversity of sport activities during adolescence predicts higher levels of leisure-time physical activity (LTPA) in adulthood. From sport activity participation reported by 17-year-old twins, we formed five groups: 1, 2, 3, 4, and 5+ different sport activities. At follow-up in their mid-thirties, twins were divided into four activity classes based on LTPA, including active commuting. Multinomial regression analyses, adjusted for several confounders, were conducted separately for male (N=1288) and female (N=1770) participants. Further, conditional logistic regression analysis included 23 twin pairs discordant for both diversity of sport activities in adolescence and LTPA in adulthood. The diversity of leisure-time sport activities in adolescence had a significant positive association with adulthood LTPA among females. Membership in the most active adult quartile, compared to the least active quartile, was predicted by participation in 2, 3, 4, and 5+ sport activities in adolescence with odds ratios: 1.52 (p=0.11), 1.86 (p=0.02), 1.29 (p=0.39), and 3.12 (p=5.4e-05), respectively. Within-pair analyses, limited by the small sample of twins discordant for both adolescent activities and adult outcomes, did not replicate the association. A greater diversity of leisure-time sport activities in adolescence predicts higher levels of LTPA in adulthood in females, but the causal nature of this association remains unresolved.
Objectives: The aim of the present study was to examine the role of genetic and environmental fac... more Objectives: The aim of the present study was to examine the role of genetic and environmental factors in the phenotypic variance of bruxism in a large population-based cohort of young adult twins in Finland. Methods: The material of the present study derives from the FinnTwin16 cohort study consisting of five birth cohorts of twin pairs born in 1975-1979 who completed a questionnaire (at mean age 24, range 23-27 years) with data on frequency of sleep-related bruxism in 2000-2002. We used quantitative genetic modeling, based on the genetic similarity of monozygotic and dizygotic twins, to estimate the most probable genetic model for bruxism, based on decomposition of phenotypic variance into components: additive genetic effects (A), dominant genetic effects (D), and non-shared environmental effects (E). Results: On average, 8.7% experienced bruxism weekly, 23.4% rarely, and 67.9% never, with no significant gender difference (p = .052). The best fitting genetic model for bruxism was the AE-model. Additive genetic effects accounted for 52% (95% CI 0.41-0.62) of the total phenotypic variance. Sex-limitation model revealed no gender differences. Conclusions: Genetic factors account for a substantial proportion of the phenotypic variation of the liability to sleep-related bruxism, with no gender difference in its genetic architecture.
Alcoholism: Clinical and Experimental Research, Jun 20, 2011
Background-Twin studies demonstrate that measures of alcohol consumption (AC) show evidence of ge... more Background-Twin studies demonstrate that measures of alcohol consumption (AC) show evidence of genetic influence, suggesting they may be useful in gene identification efforts. The extent to which these phenotypes will be informative in identifying susceptibility genes involved in alcohol dependence depends on the extent to which genetic influences are shared across measures of AC and alcohol problems. Previous studies have demonstrated that AC reported for the period of heaviest lifetime drinking shows a large degree of genetic overlap with alcohol dependence; however, many studies with genetic material assess current AC. Further, there are many different aspects of AC that can be assessed (e.g., frequency of use, quantity of use, and frequency of intoxication). Methods-Here, we use data from 2 large, independent, population-based twin samples, Finn-Twin 16 and The Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, to examine the extent to which genetic influences are shared across many different measures of AC and alcohol problems. Results-Genetic correlations across current AC measures and alcohol problems were high across both samples. However, both samples suggest a complex genetic architecture with many different genetic factors influencing various aspects of current AC and problems. Conclusions-These results suggest that careful attention must be paid to the phenotype in efforts to "replicate" genetic effects across samples or combine samples for meta-analyses of genetic effects influencing susceptibility to alcohol-related outcomes.
This is a self-archived version of an original article. This version may differ from the original... more This is a self-archived version of an original article. This version may differ from the original in pagination and typographic details.
Global emphasis on enhancing prevention and treatment strategies necessitates increased understan... more Global emphasis on enhancing prevention and treatment strategies necessitates increased understanding of biological mechanisms of psychopathology. Plasma proteomics is a powerful tool that has been applied in the context of specific mental disorders for biomarker identification. The p-factor, also known as the “general psychopathology factor”, is a concept in psychopathology suggesting that there is a common underlying factor that contributes to the development of various forms of mental disorders. It has been proposed that the p-factor can be used to understand the overall mental health status of an individual. Here we aimed to discover plasma proteins associated with the p-factor in 775 young adults in the FinnTwin12 cohort. Using liquid chromatography–tandem mass spectrometry, 14 proteins with a significant connection with the p-factor were identified, 9 of which were linked to epidermal growth factor receptor (EGFR) signalling. This exploratory study provides new insight into bi...
Aggressive behavior in school is an ongoing concern. The current focus is on specific manifestati... more Aggressive behavior in school is an ongoing concern. The current focus is on specific manifestations such as bullying, but the behavior is broad and heterogenous. Children spend a substantial amount of time in school, but their behaviors in the school setting tend to be less well characterized than at home. Because aggression may index multiple behavioral problems, we used three validated instruments to assess means, correlations and gender differences of teacher-rated aggressive behavior with co-occurring externalizing/internalizing problems and social behavior in 39,936 schoolchildren aged 7–14 from 4 population-based cohorts from Finland, the Netherlands, and the UK. Correlations of aggressive behavior were high with all other externalizing problems (r: 0.47–0.80) and lower with internalizing problems (r: 0.02–0.39). A negative association was observed with prosocial behavior (r: -0.33 to -0.54). Mean levels of aggressive behavior differed significantly by gender. Despite the hig...
Human aggression is a complex behaviour, the biological underpinnings of which remain poorly know... more Human aggression is a complex behaviour, the biological underpinnings of which remain poorly known. To gain insights into aggression biology, we studied relationships with aggression of 11 low-molecular-weight metabolites (amino acids, ketone bodies), processed using 1H nuclear magnetic resonance spectroscopy. We used a discovery sample of young adults and an independent adult replication sample. We studied 725 young adults from a population-based Finnish twin cohort born 1983–1987, with aggression levels rated in adolescence (ages 12, 14, 17) by multiple raters and blood plasma samples at age 22. Linear regression models specified metabolites as the response variable and aggression ratings as predictor variables, and included several potential confounders. All metabolites showed low correlations with aggression, with only one—3-hydroxybutyrate, a ketone body produced during fasting—showing significant (negative) associations with aggression. Effect sizes for different raters were g...
While polygenic risk scores (PRS) have been shown to predict many diseases and risk factors, the ... more While polygenic risk scores (PRS) have been shown to predict many diseases and risk factors, the potential of genomic prediction in harm caused by alcohol use has not yet been extensively studied. Here, we built a novel polygenic risk score of 1.1 million variants for alcohol consumption and studied its predictive capacity in 96,499 participants from the FinnGen study and 39,695 participants from prospective cohorts with detailed baseline data and up to 25 years of follow-up time. A 1 SD increase in the PRS was associated with 11.2 g (=0.93 drinks) higher weekly alcohol consumption (CI = 9.85–12.58 g, p = 2.3 × 10–58). The PRS was associated with alcohol-related morbidity (4785 incident events) and the risk estimate between the highest and lowest quintiles of the PRS was 1.83 (95% CI = 1.66–2.01, p = 1.6 × 10–36). When adjusted for self-reported alcohol consumption, education, marital status, and gamma-glutamyl transferase blood levels in 28,639 participants with comprehensive basel...
BackgroundTo conduct a comprehensive assessment of the association between aggression and academi... more BackgroundTo conduct a comprehensive assessment of the association between aggression and academic performance in compulsory education.MethodWe studied aggression and academic performance in over 27,000 individuals from four European twin cohorts participating in the ACTION consortium (Aggression in Children: Unraveling gene‐environment interplay to inform Treatment and InterventiON strategies). Individual level data on aggression at ages 7–16 were assessed by three instruments (Achenbach System of Empirically Based Assessment, Multidimensional Peer Nomination Inventory, Strengths and Difficulties Questionnaire) including parental, teacher and self‐reports. Academic performance was measured with teacher‐rated grade point averages (ages 12–14) or standardized test scores (ages 12–16). Random effect meta‐analytical correlations with academic performance were estimated for parental ratings (in all four cohorts) and self‐ratings (in three cohorts).ResultsAll between‐family analyses indi...
BackgroundAggression in children has genetic and environmental causes. Studies of aggression can ... more BackgroundAggression in children has genetic and environmental causes. Studies of aggression can pool existing datasets to include more complex models of social effects. Such analyses require large datasets with harmonized outcome measures. Here, we made use of a reference panel for phenotype data to harmonize multiple aggression measures in school‐aged children to jointly analyze data from five large twin cohorts.MethodsIndividual level aggression data on 86,559 children (42,468 twin pairs) were available in five European twin cohorts measured by different instruments. A phenotypic reference panel was collected which enabled a model‐based phenotype harmonization approach. A bi‐factor integration model in the integrative data analysis framework was developed to model aggression across studies while adjusting for rater, age, and sex. Finally, harmonized aggression scores were analyzed to estimate contributions of genes, environment, and social interaction to aggression. The large sam...
The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental ... more The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations.
The aim of this study was to examine the effects of genetic and environment influences and sex on... more The aim of this study was to examine the effects of genetic and environment influences and sex on injury involvement using two sets of Finnish twin data. The younger participants were 955 twins born between 1983 and 1987, aged 20 to 24 years. The older participants were 12,428 twins born between 1930 and 1957, aged 33 to 60 years. Within-twin correlations in monozygotic and dizygotic twins suggested that genetic effects play no role in injury involvement among young twins, but do have some effect at older ages. The results indicated that environmental factors have greater importance in injury involvement than genetic factors in the younger twin data set (FT12), whereas in a middle-aged (33–60 years) twin data set, genetic effects explained about quarter of the variance in injury involvement. Sex was a strong contributing factor, with males being generally more prone to injuries than females.
Alcoholism: Clinical and Experimental Research, Sep 1, 2022
BackgroundWe sought to clarify the impact of adolescent alcohol misuse on adult physical health a... more BackgroundWe sought to clarify the impact of adolescent alcohol misuse on adult physical health and subjective well‐being. To do so, we investigated both the direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction and the indirect effects on these outcomes attributable to subsequent alcohol problems.MethodThe sample included 2733 twin pairs (32% monozygotic; 52% female) from the FinnTwin16 study. Adolescent alcohol misuse was a composite of frequency of drunkenness, frequency of alcohol use, and alcohol problems at ages 16, 17, and 18.5. The early midlife outcomes included somatic symptoms, self‐rated health, and life satisfaction at age 34. The mediators examined as part of the indirect effect analyses included alcohol problems from the Rutgers Alcohol Problem Index at ages 24 and 34. Serial mediation and co‐twin comparison models were applied and included covariates from adolescence and early midlife.ResultsThere were weak direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction. However, there was stronger evidence for indirect effects, whereby young adult and early midlife alcohol problems serially mediated the relationship between adolescent alcohol misuse and early midlife somatic symptoms (β = 0.03, 95% CI [0.03, 0.04]), self‐rated health (β = −0.02, 95% CI [−0.03, −0.01]), and life satisfaction (β = −0.03, CI [−0.04, −0.02]). These serial mediation effects were robust in co‐twin comparison analyses.ConclusionsThese results provide evidence that alcohol problems are a primary driver linking adolescent alcohol misuse and poor health outcomes across the lifespan.
Aims To assess associations of intoxication frequency and number of drinks needed to become intox... more Aims To assess associations of intoxication frequency and number of drinks needed to become intoxicated in mid-adolescence with onset of psychiatric disorders in early adulthood. Design Prospective cohort study. Setting Northern Finland. Participants People from the Northern Finland Birth Cohort 1986 who self-reported adolescent alcohol use: 6,548 subjects (69.4% of the original sample). Data on alcohol use were collected using questionnaires at ages 15-16 years. Measurements Outcomes were any non-organic psychosis, mood disorder, anxiety disorder, any substance use disorder (SUD) and all the studied psychiatric disorders in early adulthood gathered from nationwide health care, pension and insurance registers. Number of drinks needed to become intoxicated was categorized into three classes: (1) No alcohol use or intoxication, and (2) low and (3) high alcohol tolerance (more than 7/9 drinks for females/males) groups. Similarly, intoxication frequency was divided into three classes: (1) never, (2) 1-2 times and (3) 3 or more times during the past 30 days. Information regarding gender, family type, other drug use, psychopathology using Youth Self-Report (YSR) total score, and parental psychiatric disorders were used as covariates. Findings In the multivariable analyses, both low [OR 3.0, 95% CI 1.3-6.7, p-value=0.009] and high [OR 4.4, 95% CI 1.8-11.1, p-value=0.001] alcohol tolerance were associated with increased risk of SUD. More frequent intoxication was associated with increased frequency of SUD [OR 3.9, 95% CI 2.0-7.3, p-value<0.
Alcoholism: Clinical and Experimental Research, Apr 4, 2011
Background-Long-term functional brain effects of adolescent alcohol abuse remain uncertain, parti... more Background-Long-term functional brain effects of adolescent alcohol abuse remain uncertain, partially because of difficulties in distinguishing inherited deficits from neuronal effects of ethanol and by confounds associated with alcohol abuse, especially nicotine exposure. We conducted a longitudinal twin study to determine neurocognitive effects of adolescent alcohol abuse, as measured with the auditory event-related potential (ERP) component P3, a putative marker of genetic vulnerability to alcoholism. Methods-Twin pairs (N = 177; 150 selected for intrapair concordance/ discordance for alcoholrelated problems at age 18½) were recruited from ongoing studies of twins born 1975-1979 in Finland. Alcohol and tobacco use were assessed with questionnaires at ages 16, 17, 18½, and ∼25, and by a structured psychiatric interview concurrent with the ERP testing at mean age 25.8. During ERP recordings, subjects were instructed to detect target tones within a train of frequent "standards" and to ignore occasional "novel" sounds. To distinguish familial factors from ethanol effects, ERP and self-reported alcohol use measures were incorporated into hierarchical multiple regression (HMR) analysis, and intrapair differences in ERP were associated with intrapair differences in alcohol variables. Results-Novel-sound P3 amplitude correlated negatively with self-reported alcohol use in both between-and within-family analyses. No similar effect was observed for target-tone P3. HMR results suggest that twins' similarity for novel-sound P3 amplitude is modulated by their alcohol use, and this effect of alcohol use is influenced by genetic factors. Conclusions-Our results, from a large sample of twins selected from a population-based registry for pairwise concordance/discordance for alcohol problems at 18½, demonstrate that adolescent alcohol abuse is associated with subtle neurophysiological changes in attention and orienting. The changes are reflected in decreased novel-sound P3 amplitude and may be modified by genetic factors.
This is a self-archived version of an original article. This version may differ from the original... more This is a self-archived version of an original article. This version may differ from the original in pagination and typographic details.
The factor mixture model (FMM) uses a hybrid of both categorical and continuous latent variables.... more The factor mixture model (FMM) uses a hybrid of both categorical and continuous latent variables. The FMM is a good model for the underlying structure of psychopathology because the use of both categorical and continuous latent variables allows the structure to be simultaneously categorical and dimensional. This is useful because both diagnostic class membership and the range of severity within and across diagnostic classes can be modeled concurrently. While the conceptualization of the FMM has been explained in the literature, the use of the FMM is still not prevalent. One reason is that there is little research about how such models should be applied in practice and, once a well fitting model is obtained, how it should be interpreted. In this paper, the FMM will be explored by studying a real data example on conduct disorder. By exploring this example, this paper aims to explain the different formulations of the FMM, the various steps in building a FMM, as well as how to decide between a FMM and alternative models. In recent years there has been a debate in the psychological literature about whether the underlying structure of psychological disorders, such as conduct disorder, is categorical or dimensional. In the categorical view, psychological disorders are represented by diagnostic categories that indicate whether a person is affected or unaffected by a disorder and/or whether a person has a specific subtype. This has been the predominant view of psychopathology because it has the advantage of meeting clinical needs and the needs of reporting for health care planners and insurance companies (Muthén, 2006). Alternatively, psychological disorders are considered dimensional in nature and are represented as a continuous distribution, with each individual having some amount of the disorder. The advantage of the dimensional view is that each disorder can be represented as a quantitative
Background-In 1990, Blum and colleagues first reported an association between DRD2 and alcoholism... more Background-In 1990, Blum and colleagues first reported an association between DRD2 and alcoholism. While there have been subsequent replications of this genetic association, there have also been numerous studies that failed to detect an association between DRD2 and alcohol dependence. We propose that one aspect contributing to this inconsistency is the variation in alcohol phenotype used across studies. Methods-Within the population based Finnish twin sample, FinnTwin16, we previously performed multivariate twin analyses to extract latent genetic factors which account for the variation across seven measures of alcohol consumption (frequency of drinking, frequency × quantity, frequency of heavy drinking, frequency of intoxication, and maximum drinks in a 24 hour period) and problems (the Rutgers Alcohol Problem Index-RAPI and the Mälmö-modified Michigan Alcohol Screen Test-MmMAST) in 3,065 twins. In the present study, we examined the association between thirty-one DRD2/ANKK1 SNPs and the genetic factor scores generated by twin analyses in a subset of FinnTwin16 (n=602). We focus on two of the genetic factors: a general alcohol consumption and problems factor score which represents shared genetic variance across alcohol measures, and an alcohol problems genetic factor score which loads onto the two indices of problematic drinking (MAST and RAPI). Results-After correction for multiple testing across SNPs and phenotypes, of the thirty-one SNPs genotyped across DRD2/ANKK1, one SNP (rs10891549) showed significant association with the general alcohol consumption and problems factor score (p=0.004), and four SNPs (rs10891549, rs1554929, rs6275, rs6279), representing 2 independent signals after accounting for LD, showed significant association with the alcohol problems genetic factor score (p=0.005, p=0.005, p=0.003, p=0.003). Conclusions-In this study, we provide additional positive evidence for the association between DRD2/ANKK1 and alcohol outcomes, including frequency of drinking and drinking problems. Additionally, post hoc analyses indicate stronger association signals using genetic factor scores than individual measures, which suggests that accounting for the genetic architecture of the alcohol measures reduces genetic heterogeneity in alcohol dependence outcomes in this sample and enhances the ability to detect association.
Robust sex differences in some spatial abilities that favor males have raised the question of whe... more Robust sex differences in some spatial abilities that favor males have raised the question of whether testosterone contributes to those differences. There is some evidence for prenatal organizational effects of testosterone on male-favoring spatial abilities, but not much is known about the role of pubertal testosterone levels on adult cognitive abilities. We studied the association between pubertal testosterone (at age 14) and cognitive performance in young adulthood (at age 21-23), assessing male-favoring, female-favoring, and sex-neutral cognitive domains in a population-based sample of 130 male and 178 female twins. Pubertal testosterone was negatively associated with performance in the Mental Rotation Test in young adult men (r = −.27), while among women no significant associations between testosterone and cognitive measures were detected. The significant association among men remained after controlling for pubertal development. Confirmatory within-family comparisons with one-sided significance testing yielded a negative correlation between twin pair differences in testosterone levels and Mental Rotation Test performances in 35 male twin pairs (r = −.32):the twin brother with higher testosterone performed less well on the Mental Rotation Test. That association was evident in18 pairs of dizygotic male twin pairs (r = −.42; analysis controlling for shared environmental effects). In contrast, the association of differences was not evident among 17 monozygotic male twin pairs (r = −.07; analysis controlling for shared genetic influences). Results suggest that pubertal testosterone levels are related specifically to male-favoring spatial ability and only among men. Within-family analyses implicated possible shared genetic effects between pubertal testosterone and mental rotation ability.
Scandinavian Journal of Medicine & Science in Sports, Jan 20, 2017
Because sustained physical activity is important for a healthy life, this paper examined whether ... more Because sustained physical activity is important for a healthy life, this paper examined whether a greater diversity of sport activities during adolescence predicts higher levels of leisure-time physical activity (LTPA) in adulthood. From sport activity participation reported by 17-year-old twins, we formed five groups: 1, 2, 3, 4, and 5+ different sport activities. At follow-up in their mid-thirties, twins were divided into four activity classes based on LTPA, including active commuting. Multinomial regression analyses, adjusted for several confounders, were conducted separately for male (N=1288) and female (N=1770) participants. Further, conditional logistic regression analysis included 23 twin pairs discordant for both diversity of sport activities in adolescence and LTPA in adulthood. The diversity of leisure-time sport activities in adolescence had a significant positive association with adulthood LTPA among females. Membership in the most active adult quartile, compared to the least active quartile, was predicted by participation in 2, 3, 4, and 5+ sport activities in adolescence with odds ratios: 1.52 (p=0.11), 1.86 (p=0.02), 1.29 (p=0.39), and 3.12 (p=5.4e-05), respectively. Within-pair analyses, limited by the small sample of twins discordant for both adolescent activities and adult outcomes, did not replicate the association. A greater diversity of leisure-time sport activities in adolescence predicts higher levels of LTPA in adulthood in females, but the causal nature of this association remains unresolved.
Objectives: The aim of the present study was to examine the role of genetic and environmental fac... more Objectives: The aim of the present study was to examine the role of genetic and environmental factors in the phenotypic variance of bruxism in a large population-based cohort of young adult twins in Finland. Methods: The material of the present study derives from the FinnTwin16 cohort study consisting of five birth cohorts of twin pairs born in 1975-1979 who completed a questionnaire (at mean age 24, range 23-27 years) with data on frequency of sleep-related bruxism in 2000-2002. We used quantitative genetic modeling, based on the genetic similarity of monozygotic and dizygotic twins, to estimate the most probable genetic model for bruxism, based on decomposition of phenotypic variance into components: additive genetic effects (A), dominant genetic effects (D), and non-shared environmental effects (E). Results: On average, 8.7% experienced bruxism weekly, 23.4% rarely, and 67.9% never, with no significant gender difference (p = .052). The best fitting genetic model for bruxism was the AE-model. Additive genetic effects accounted for 52% (95% CI 0.41-0.62) of the total phenotypic variance. Sex-limitation model revealed no gender differences. Conclusions: Genetic factors account for a substantial proportion of the phenotypic variation of the liability to sleep-related bruxism, with no gender difference in its genetic architecture.
Alcoholism: Clinical and Experimental Research, Jun 20, 2011
Background-Twin studies demonstrate that measures of alcohol consumption (AC) show evidence of ge... more Background-Twin studies demonstrate that measures of alcohol consumption (AC) show evidence of genetic influence, suggesting they may be useful in gene identification efforts. The extent to which these phenotypes will be informative in identifying susceptibility genes involved in alcohol dependence depends on the extent to which genetic influences are shared across measures of AC and alcohol problems. Previous studies have demonstrated that AC reported for the period of heaviest lifetime drinking shows a large degree of genetic overlap with alcohol dependence; however, many studies with genetic material assess current AC. Further, there are many different aspects of AC that can be assessed (e.g., frequency of use, quantity of use, and frequency of intoxication). Methods-Here, we use data from 2 large, independent, population-based twin samples, Finn-Twin 16 and The Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, to examine the extent to which genetic influences are shared across many different measures of AC and alcohol problems. Results-Genetic correlations across current AC measures and alcohol problems were high across both samples. However, both samples suggest a complex genetic architecture with many different genetic factors influencing various aspects of current AC and problems. Conclusions-These results suggest that careful attention must be paid to the phenotype in efforts to "replicate" genetic effects across samples or combine samples for meta-analyses of genetic effects influencing susceptibility to alcohol-related outcomes.
This is a self-archived version of an original article. This version may differ from the original... more This is a self-archived version of an original article. This version may differ from the original in pagination and typographic details.
Global emphasis on enhancing prevention and treatment strategies necessitates increased understan... more Global emphasis on enhancing prevention and treatment strategies necessitates increased understanding of biological mechanisms of psychopathology. Plasma proteomics is a powerful tool that has been applied in the context of specific mental disorders for biomarker identification. The p-factor, also known as the “general psychopathology factor”, is a concept in psychopathology suggesting that there is a common underlying factor that contributes to the development of various forms of mental disorders. It has been proposed that the p-factor can be used to understand the overall mental health status of an individual. Here we aimed to discover plasma proteins associated with the p-factor in 775 young adults in the FinnTwin12 cohort. Using liquid chromatography–tandem mass spectrometry, 14 proteins with a significant connection with the p-factor were identified, 9 of which were linked to epidermal growth factor receptor (EGFR) signalling. This exploratory study provides new insight into bi...
Aggressive behavior in school is an ongoing concern. The current focus is on specific manifestati... more Aggressive behavior in school is an ongoing concern. The current focus is on specific manifestations such as bullying, but the behavior is broad and heterogenous. Children spend a substantial amount of time in school, but their behaviors in the school setting tend to be less well characterized than at home. Because aggression may index multiple behavioral problems, we used three validated instruments to assess means, correlations and gender differences of teacher-rated aggressive behavior with co-occurring externalizing/internalizing problems and social behavior in 39,936 schoolchildren aged 7–14 from 4 population-based cohorts from Finland, the Netherlands, and the UK. Correlations of aggressive behavior were high with all other externalizing problems (r: 0.47–0.80) and lower with internalizing problems (r: 0.02–0.39). A negative association was observed with prosocial behavior (r: -0.33 to -0.54). Mean levels of aggressive behavior differed significantly by gender. Despite the hig...
Human aggression is a complex behaviour, the biological underpinnings of which remain poorly know... more Human aggression is a complex behaviour, the biological underpinnings of which remain poorly known. To gain insights into aggression biology, we studied relationships with aggression of 11 low-molecular-weight metabolites (amino acids, ketone bodies), processed using 1H nuclear magnetic resonance spectroscopy. We used a discovery sample of young adults and an independent adult replication sample. We studied 725 young adults from a population-based Finnish twin cohort born 1983–1987, with aggression levels rated in adolescence (ages 12, 14, 17) by multiple raters and blood plasma samples at age 22. Linear regression models specified metabolites as the response variable and aggression ratings as predictor variables, and included several potential confounders. All metabolites showed low correlations with aggression, with only one—3-hydroxybutyrate, a ketone body produced during fasting—showing significant (negative) associations with aggression. Effect sizes for different raters were g...
While polygenic risk scores (PRS) have been shown to predict many diseases and risk factors, the ... more While polygenic risk scores (PRS) have been shown to predict many diseases and risk factors, the potential of genomic prediction in harm caused by alcohol use has not yet been extensively studied. Here, we built a novel polygenic risk score of 1.1 million variants for alcohol consumption and studied its predictive capacity in 96,499 participants from the FinnGen study and 39,695 participants from prospective cohorts with detailed baseline data and up to 25 years of follow-up time. A 1 SD increase in the PRS was associated with 11.2 g (=0.93 drinks) higher weekly alcohol consumption (CI = 9.85–12.58 g, p = 2.3 × 10–58). The PRS was associated with alcohol-related morbidity (4785 incident events) and the risk estimate between the highest and lowest quintiles of the PRS was 1.83 (95% CI = 1.66–2.01, p = 1.6 × 10–36). When adjusted for self-reported alcohol consumption, education, marital status, and gamma-glutamyl transferase blood levels in 28,639 participants with comprehensive basel...
BackgroundTo conduct a comprehensive assessment of the association between aggression and academi... more BackgroundTo conduct a comprehensive assessment of the association between aggression and academic performance in compulsory education.MethodWe studied aggression and academic performance in over 27,000 individuals from four European twin cohorts participating in the ACTION consortium (Aggression in Children: Unraveling gene‐environment interplay to inform Treatment and InterventiON strategies). Individual level data on aggression at ages 7–16 were assessed by three instruments (Achenbach System of Empirically Based Assessment, Multidimensional Peer Nomination Inventory, Strengths and Difficulties Questionnaire) including parental, teacher and self‐reports. Academic performance was measured with teacher‐rated grade point averages (ages 12–14) or standardized test scores (ages 12–16). Random effect meta‐analytical correlations with academic performance were estimated for parental ratings (in all four cohorts) and self‐ratings (in three cohorts).ResultsAll between‐family analyses indi...
BackgroundAggression in children has genetic and environmental causes. Studies of aggression can ... more BackgroundAggression in children has genetic and environmental causes. Studies of aggression can pool existing datasets to include more complex models of social effects. Such analyses require large datasets with harmonized outcome measures. Here, we made use of a reference panel for phenotype data to harmonize multiple aggression measures in school‐aged children to jointly analyze data from five large twin cohorts.MethodsIndividual level aggression data on 86,559 children (42,468 twin pairs) were available in five European twin cohorts measured by different instruments. A phenotypic reference panel was collected which enabled a model‐based phenotype harmonization approach. A bi‐factor integration model in the integrative data analysis framework was developed to model aggression across studies while adjusting for rater, age, and sex. Finally, harmonized aggression scores were analyzed to estimate contributions of genes, environment, and social interaction to aggression. The large sam...
The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental ... more The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations.
The aim of this study was to examine the effects of genetic and environment influences and sex on... more The aim of this study was to examine the effects of genetic and environment influences and sex on injury involvement using two sets of Finnish twin data. The younger participants were 955 twins born between 1983 and 1987, aged 20 to 24 years. The older participants were 12,428 twins born between 1930 and 1957, aged 33 to 60 years. Within-twin correlations in monozygotic and dizygotic twins suggested that genetic effects play no role in injury involvement among young twins, but do have some effect at older ages. The results indicated that environmental factors have greater importance in injury involvement than genetic factors in the younger twin data set (FT12), whereas in a middle-aged (33–60 years) twin data set, genetic effects explained about quarter of the variance in injury involvement. Sex was a strong contributing factor, with males being generally more prone to injuries than females.
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