Basic or Adaptation: The Assessment and Heritability of a Brief Measure of Agency.

The interpersonal circumplex describes two major axes of personality that guide much of social behavior. Agency, one half of the interpersonal circumplex, refers to relatively stable behavioral patterns that center on self-focused dominance and assertiveness. Past empirical work on agency tends to treat the dimension as a characteristic adaptation, rather than a basic component of personality, in part due to the relatively large gender difference in agency with masculine individuals tending to behave more agentic. However, the psychometric overlap between agency and the most closely linked big five dimension, extraversion, is not well-established, and no behavior genetic work has documented evidence concerning the role of genetic and environmental influences. It is unclear whether agency is more similar to a personality trait, with no evidence of shared environmental influence and moderate heritability, or a characteristic adaptation, with some evidence for shared environmental influence and possibly lower heritability. We used the Midlife Development in the United States study to examine agency, big five, and generativity with replication and robustness check (Nnon-twins = 5,194; Ntwins = 1,914; NMilwaukee = 592). Results indicated that agency was higher in men (d = -.24), moderately heritable (44.4%), strongly correlated with extraversion (r = .51), moderately correlated with generativity (r = .36), and that approximately 40% of the variance in agency was shared with the big five. Agency also changed strongly with extraversion and openness, but less so generativity. Altogether, these results indicate that agency functions similar to other basic personality dimensions but is not clearly a dispositional trait.

Exploring the utility of current polygenic scores in capturing resilience.

Although resilience has been identified to be moderately heritable, little is known about the genetic variants involved. While there has not yet been a robust genome-wide association study (GWAS) of resilience, existing GWAS of related phenotypes may provide a starting point for developing our understanding of the heritability of resilience. In a sample of older, US adults (N = 9480), we examined the extent to which proxy polygenic scores (PGS) explained the variance in resilience. Four of the 32 PGS assessed (subjective wellbeing, neuroticism, depressive symptoms and educational attainment) reached significance among participants with European ancestries, but with relatively small effects (= 0.002-0.09). Notably, PGSs derived from GWAS of PTSD among participants with either European or African ancestries were uncorrelated with resilience. Even aggregated across all available proxy PGSs, existing PGSs are not sufficient to inform our understanding of the genetics underlying the heritability of resilience. A large-scale GWAS of resilience is needed as it would provide greater insight into the genetic mechanisms underlying the heritability of resilience.

Author Correction: GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability.

Several occurrences of the word 'schizophrenia' have been re-worded as 'liability to schizophrenia' or 'schizophrenia risk', including in the title, which should have been "GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability," as well as in Supplementary Figures 1-10 and Supplementary Tables 7-10, to more accurately reflect the findings of the work.

Imputation of behavioral candidate gene repeat variants in 486,551 publicly-available UK Biobank individuals.

Some of the most widely studied variants in psychiatric genetics include variable number tandem repeat variants (VNTRs) in SLC6A3, DRD4, SLC6A4, and MAOA. While initial findings suggested large effects, their importance with respect to psychiatric phenotypes is the subject of much debate with broadly conflicting results. Despite broad interest, these loci remain absent from the largest available samples, such as the UK Biobank, limiting researchers' ability to test these contentious hypotheses rigorously in large samples. Here, using two independent reference datasets, we report out-of-sample imputation accuracy estimates of >0.96 for all four VNTR variants and one modifying SNP, depending on the reference and target dataset. We describe the imputation procedures of these candidate variants in 486,551 UK Biobank individuals, and have made the imputed variant data available to UK Biobank researchers. This resource, provided to the scientific community, will allow the most rigorous tests to-date of the roles of these variants in behavioral and psychiatric phenotypes.

Interpreting Behavior Genetic Models: Seven Developmental Processes to Understand.

Behavior genetic findings figure in debates ranging from urgent public policy matters to perennial questions about the nature of human agency. Despite a common set of methodological tools, behavior genetic studies approach scientific questions with potentially divergent goals. Some studies may be interested in identifying a complete model of how individual differences come to be (e.g., identifying causal pathways among genotypes, environments, and phenotypes across development). Other studies place primary importance on developing models with predictive utility, in which case understanding of underlying causal processes is not necessarily required. Although certainly not mutually exclusive, these two goals often represent tradeoffs in terms of costs and benefits associated with various methodological approaches. In particular, given that most empirical behavior genetic research assumes that variance can be neatly decomposed into independent genetic and environmental components, violations of model assumptions have different consequences for interpretation, depending on the particular goals. Developmental behavior genetic theories postulate complex transactions between genetic variation and environmental experiences over time, meaning assumptions are routinely violated. Here, we consider two primary questions: (1) How might the simultaneous operation of several mechanisms of gene-environment (GE)-interplay affect behavioral genetic model estimates? (2) At what level of GE-interplay does the 'gloomy prospect' of unsystematic and non-replicable genetic associations with a phenotype become an unavoidable certainty?

You have to follow through: Attaining behavioral change goals predicts volitional personality change.

Prior research has found that people's desires to change their personality traits predict corresponding subsequent trait growth over time. However, few studies have examined the processes through which people can volitionally change their personality traits. Thus, it remains unclear whether merely desiring change predicts trait growth or whether actively pursuing change is necessary. The present study was a 15-week intensive longitudinal design that tested whether engaging in trait-typical behaviors predicted trait change. Participants provided self-report ratings of their personality traits and were able to freely accept and complete weekly "challenges"-prewritten behavioral goals that would pull their thoughts, feelings, and behaviors in line with their desired traits. Results indicated that merely accepting behavioral challenges did not predict trait changes. Rather, only actually completing challenges (i.e., performing trait-typical behaviors) predicted trait change over time. Thus, merely wanting to change does not appear to be sufficient to evoke trait growth; successfully changing one's personality traits may require actively and successfully implementing behaviors to change oneself. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia.

Cannabis use is a heritable trait that has been associated with adverse mental health outcomes. In the largest genome-wide association study (GWAS) for lifetime cannabis use to date (N = 184,765), we identified eight genome-wide significant independent single nucleotide polymorphisms in six regions. All measured genetic variants combined explained 11% of the variance. Gene-based tests revealed 35 significant genes in 16 regions, and S-PrediXcan analyses showed that 21 genes had different expression levels for cannabis users versus nonusers. The strongest finding across the different analyses was CADM2, which has been associated with substance use and risk-taking. Significant genetic correlations were found with 14 of 25 tested substance use and mental health-related traits, including smoking, alcohol use, schizophrenia and risk-taking. Mendelian randomization analysis showed evidence for a causal positive influence of schizophrenia risk on cannabis use. Overall, our study provides new insights into the etiology of cannabis use and its relation with mental health.

Genetic and Environmental Pathways Underlying Personality Traits and Perceived Stress: Concurrent and Longitudinal Twin Studies.

The present study examined the genetic and environmental etiology underlying the Big Five personality traits and perceived stress, concurrently and longitudinally. In study 1, we used the twin sample from the National Longitudinal Study of Adolescent to Adult Health (Add Health IV) data. The results indicated that about 70% of the association between the Big Five personality traits and perceived stress was due to genetic influences. In study 2, we used the twin sample from the Midlife in the United States Survey (MIDUS I and II) to examine the genetic and environmental influences underlying the longitudinal relations between the Big Five personality traits and perceived stress. The results suggested that continuity in perceived stress was primarily accounted for by genetic influences, and changes in perceived stress were mainly due to nonshared environmental influences. The continuity in the association between the five personality traits and perceived stress was largely accounted for by genetic factors, and nonshared environmental factors made greater contributions to changes in the association between personality traits and perceived stress. Among the Big Five personality traits, the genetic components in conscientiousness and neuroticism made substantial contributions to the genetic link between personality traits and perceived stress across both studies.

Predicting Cognitive Executive Functioning with Polygenic Risk Scores for Psychiatric Disorders.

Executive functions (EFs) have been proposed as an endophenotype for psychopathology because EF deficits are associated with most psychiatric disorders. To examine this hypothesis, we derived polygenic risk scores for autism, attention-deficit/hyperactive disorder (ADHD), bipolar disorder, major depression (MDD), and schizophrenia, using genome-wide data from the Psychiatric Genomics Consortium as discovery samples. We then examined the relationships between these polygenic risk scores and three separable EF components measured with a latent variable model. We also examined the relationship between genetic risk for ADHD and MDD and their respective symptom counts and lifetime diagnoses. We found no evidence for larger effect sizes for EFs as endophenotypes for psychiatric disorders. However, larger sample sizes will be important in examining this relationship further.

Genome-wide association study identifies 74 loci associated with educational attainment.

Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.

Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses.

Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.

Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium.

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.

Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder.

IMPORTANCE: Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases). OBJECTIVES: To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. DESIGN, SETTING, AND PARTICIPANTS: Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63,661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. MAIN OUTCOMES AND MEASURES: Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. RESULTS: A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 × 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 × 10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 × 10-12 < P < .05) and MDD (4.02 × 10-9 < P < .05) in the 2 other cohorts. CONCLUSIONS AND RELEVANCE: This study identifies a novel locus for neuroticism. The variant is located in a known gene that has been associated with bipolar disorder and schizophrenia in previous studies. In addition, the study shows that neuroticism is influenced by many genetic variants of small effect that are either common or tagged by common variants. These genetic variants also influence MDD. Future studies should confirm the role of the MAGI1 locus for neuroticism and further investigate the association of MAGI1 and the polygenic association to a range of other psychiatric disorders that are phenotypically correlated with neuroticism.

Genome-Wide Association Study of Behavioral Disinhibition in a Selected Adolescent Sample.

Behavioral disinhibition (BD) is a quantitative measure designed to capture the heritable variation encompassing risky and impulsive behaviors. As a result, BD represents an ideal target for discovering genetic loci that predispose individuals to a wide range of antisocial behaviors and substance misuse that together represent a large cost to society as a whole. Published genome-wide association studies (GWAS) have examined specific phenotypes that fall under the umbrella of BD (e.g. alcohol dependence, conduct disorder); however no GWAS has specifically examined the overall BD construct. We conducted a GWAS of BD using a sample of 1,901 adolescents over-selected for characteristics that define high BD, such as substance and antisocial behavior problems, finding no individual locus that surpassed genome-wide significance. Although no single SNP was significantly associated with BD, restricted maximum likelihood analysis estimated that 49.3 % of the variance in BD within the Caucasian sub-sample was accounted for by the genotyped SNPs (p = 0.06). Gene-based tests identified seven genes associated with BD (p ≤ 2.0 × 10(-6)). Although the current study was unable to identify specific SNPs or pathways with replicable effects on BD, the substantial sample variance that could be explained by all genotyped SNPs suggests that larger studies could successfully identify common variants associated with BD.

Common genetic variants associated with cognitive performance identified using the proxy-phenotype method.

We identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxy-phenotype method. First, we conduct a genome-wide association study of educational attainment in a large sample (n = 106,736), which produces a set of 69 education-associated SNPs. Second, using independent samples (n = 24,189), we measure the association of these education-associated SNPs with cognitive performance. Three SNPs (rs1487441, rs7923609, and rs2721173) are significantly associated with cognitive performance after correction for multiple hypothesis testing. In an independent sample of older Americans (n = 8,652), we also show that a polygenic score derived from the education-associated SNPs is associated with memory and absence of dementia. Convergent evidence from a set of bioinformatics analyses implicates four specific genes (KNCMA1, NRXN1, POU2F3, and SCRT). All of these genes are associated with a particular neurotransmitter pathway involved in synaptic plasticity, the main cellular mechanism for learning and memory.

Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory.

Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.

GWAS of 126,559 individuals identifies genetic variants associated with educational attainment.

A genome-wide association study (GWAS) of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490. Three independent single-nucleotide polymorphisms (SNPs) are genome-wide significant (rs9320913, rs11584700, rs4851266), and all three replicate. Estimated effects sizes are small (coefficient of determination R(2) ≈ 0.02%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for ≈2% of the variance in both educational attainment and cognitive function. Genes in the region of the loci have previously been associated with health, cognitive, and central nervous system phenotypes, and bioinformatics analyses suggest the involvement of the anterior caudate nucleus. These findings provide promising candidate SNPs for follow-up work, and our effect size estimates can anchor power analyses in social-science genetics.

Measurement invariance of DSM-IV alcohol, marijuana and cocaine dependence between community-sampled and clinically overselected studies.

AIMS: To examine whether DSM-IV symptoms of substance dependence are psychometrically equivalent between existing community-sampled and clinically overselected studies. PARTICIPANTS: A total of 2476 adult twins born in Minnesota and 4121 unrelated adult participants from a case-control study of alcohol dependence. MEASUREMENTS: Life-time DSM-IV alcohol, marijuana and cocaine dependence symptoms and ever use of each substance. DESIGN: We fitted a hierarchical model to the data, in which ever use and dependence symptoms for each substance were indicators of alcohol, marijuana or cocaine dependence which were, in turn, indicators of a multi-substance dependence factor. We then tested the model for measurement invariance across participant groups, defined by study source and participant sex. FINDINGS: The hierarchical model fitted well among males and females within each sample [comparative fit index (CFI) > 0.96, Tucker-Lewis index (TLI) > 0.95 and root mean square error of approximation (RMSEA) < 0.04 for all], and a multi-group model demonstrated that model parameters were equivalent across sample- and sex-defined groups (ΔCFI = 0.002 between constrained and unconstrained models). Differences between groups in symptom endorsement rates could be expressed solely as mean differences in the multi-substance dependence factor. CONCLUSIONS: Life-time substance dependence symptoms fitted a dimensional model well. Although clinically overselected participants endorsed more dependence symptoms, on average, than community-sampled participants, the pattern of symptom endorsement was similar across groups. From a measurement perspective, DSM-IV criteria are equally appropriate for describing substance dependence across different sampling methods.