In celebration of Matt McGue’s career, we conducted a longitudinal extension of a simple and elegant study he supervised nearly two decades ago (Keyes et al. 2008). We examined the effects of teenage exposure to parental smoking on substance use and externalizing outcomes in an adoption study. In total, 1232 offspring from 617 families were longitudinally assessed at mean ages of 15, 18, 22, and 32 years, with 37

Personality traits describe stable differences in how people think, feel and behave, and how they interact with and experience their social and physical environments1,2. Many questions remain unanswered about associations between DNA and personality traits, such as their robustness, their generalizability and the biological and social pathways through which they act. Here we meta-analyse data across 46 cohorts comprising 611,037 to 1.14 million participants with European-like and African-like genomes for genome-wide association studies (GWAS) of the Big Five personality traits (extraversion, agreeableness, conscientiousness, neuroticism and openness to experience), and data from up to 50,725 participants for within-family GWAS. We identify 1,260 lead genetic variants associated with personality, including 824 novel variants3. Common genetic variants explain a moderate 4.8-9.3% of the variance in measures of each trait, and 9.3-13.3% among instruments with typical measurement reliability. Genetic associations with personality are highly consistent but not identical across geography, reporter (self versus close other), age group and measurement instrument, and we find minimal spousal assortment for personality in recent history. In contrast to many other social and behavioural traits4,5, within-family GWAS and polygenic index analyses indicate that genetic associations with personality are minimally confounded by the shared family environment. Polygenic prediction, genetic correlation and Mendelian randomization analyses indicate that personality traits have widespread, potentially causal associations with consequential behaviours and life outcomes. Overall, we find that the genetic architecture of personality is robustly generalizable, minimally confounded and widely relevant to human experience.

Matt McGue's research has made intelligence a model case for the explanatory reach of behavioral genetics. His early studies, conducted with Thomas Bouchard and other collaborators, on twins and other kinships demonstrated that cognitive ability is substantially heritable, and later analyses showed that this influence increases from childhood to adulthood and remains appreciable in late life, while shared environmental effects diminish. McGue and colleagues also extended twin and adoption methods to the study of educational attainment and social mobility, demonstrating that cognitive ability, noncognitive traits, and family background all contribute, and that higher education seems to benefit individuals across the ability spectrum. Because intelligence is uniquely scrutinized, the credibility of these findings depends on the soundness of the adoption design. A persistent critique is that adoption agencies engage in various forms of selection, leading to restriction of range in environmental quality and the confounding of genetic and environmental influences. McGue and colleagues addressed some of these concerns in their Minnesota studies, most notably showing that a correction for restriction of range did not appreciably alter the correlation between adoptive siblings in IQ. The present paper reviews McGue's accomplishments and reports new results about selective placement based on the correlations between parental phenotypes and the polygenic scores of their adopted offspring.

While genetic influences on general intelligence have been well documented, less is known about the genetics underlying narrower abilities (“group factors”). By applying structural equation modeling to results from several genome-wide association studies (GWAS), most critically of self-reported math ability (N = 564 698) and highest math class taken (N = 430 445), we identified 53 single-nucleotide polymorphisms (SNPs) associated with a latent trait, orthogonal by design with general intelligence, approximating the group factor of quantitative ability. The genes near these SNPs implicated the biological process of neuron projection development, and the genome-wide pattern of gene-set enrichment affirmed the involvement of brain development and synaptic function. We calculated a number of genetic correlations with this quantitative factor, finding negative associations with both internalizing and externalizing disorders and positive associations with STEM occupations such as computer programming. These results provide further evidence for genetic influences on traits other than general factors in human behavioral variation, point to the mechanisms mediating these genetic influences on quantitative ability and interests, and affirm the relationships of the latter traits with a number of real-world outcomes.

A genome-wide association study (GWAS) tests whether each of several million sites in the human genome is correlated with a trait of interest. For a number of reasons, including replication of GWAS results within families, we can be confident that significant correlations reflect in part the causal effects of DNA-level variation on the studied trait. This level of causal inference, much stronger than in most observational studies, enables some far-reaching conclusions about the antecedents and structure of human intelligence. We discuss some of these conclusions regarding whether brain size affects intelligence and the long-debated issue of how different intelligence tests are related to each other.

Philosophers and psychologists alike have long debated the etiology of beliefs about human agency. Recently, empirical investigations have shown that lay beliefs about free will and determinism represent stable and important individual differences. Despite a perennial interest in the sources of agentic belief, genetic and environmental influences on such beliefs have never been studied. We administered a battery of items assessing these beliefs to a unique sample of 394 adoptive and biological families with adult offspring to investigate the origins of agentic beliefs and their relationships. We found significant differences between adopted and biological offspring and between the parents of such children, particularly in beliefs about determinism. Biometric modeling revealed especially surprising results: unlike the vast majority of traits studied in family designs, agentic beliefs appear to be weakly or not at all heritable. Since genetic factors might be regarded as typical of the "initial conditions" in philosophical thought experiments about free will and determinism, it is especially ironic that beliefs about free will and determinism may be among the traits least influenced by genetic differences.

Genome-wide association studies (GWAS) have discovered thousands of replicable genetic associations, guiding drug target discovery and powering genetic prediction of human phenotypes and diseases. However, genetic associations can be affected by gene-environment correlations and non-random mating, which can lead to biased inferences in downstream analyses. Family-based GWAS (FGWAS) uses the natural experiment of random assignment of genotype within families to separate out the contribution of direct genetic effects (DGEs) - causal effects of alleles in an individual on an individual - from other factors contributing to genetic associations. Here, we report results from an FGWAS meta-analysis of 34 phenotypes from 17 cohorts. We found evidence that factors uncorrelated with DGEs make substantial contributions to genetic associations for 27 phenotypes, with population stratification confounding - a form of gene-environment correlation - likely the major cause. By estimating SNP heritability and genetic correlations using DGEs, we found evidence that assortative mating has led to overestimation of SNP heritability for 5 phenotypes and overestimation of the degree of shared genetic effects (pleiotropy) between 22 pairs of phenotypes. Polygenic predictors constructed from DGEs are particularly useful for studying natural selection, assortative mating, and indirect genetic effects (effects of relatives' genes mediated through the family environment). We validate our meta-analysis results by predicting phenotypes in hold-out samples using polygenic predictors constructed from DGEs, achieving statistically significant out-of-sample prediction for 24 phenotypes with little attenuation of predictive power within-families. We provide FGWAS summary statistics for 34 phenotypes that can be used for downstream analyses. Our study provides both a template for performing FGWAS and an argument for its value for debiasing inferences and understanding the impact of environment and mating patterns.

We conducted a genome-wide association study on income among individuals of European descent (N = 668,288) to investigate the relationship between socio-economic status and health disparities. We identified 162 genomic loci associated with a common genetic factor underlying various income measures, all with small effect sizes (the Income Factor). Our polygenic index captures 1-5% of income variance, with only one fourth due to direct genetic effects. A phenome-wide association study using this index showed reduced risks for diseases including hypertension, obesity, type 2 diabetes, depression, asthma and back pain. The Income Factor had a substantial genetic correlation (0.92, s.e. = 0.006) with educational attainment. Accounting for the genetic overlap of educational attainment with income revealed that the remaining genetic signal was linked to better mental health but reduced physical health and increased risky behaviours such as drinking and smoking. These findings highlight the complex genetic influences on income and health.

Personality traits describe stable differences in how individuals think, feel, and behave and how they interact with and experience their social and physical environments. We assemble data from 46 cohorts including 611K-1.14M participants with European-like and African-like genomes for genome-wide association studies (GWAS) of the Big Five personality traits (extraversion, agreeableness, conscientiousness, neuroticism, and openness to experience), and data from 51K participants for within-family GWAS. We identify 1,257 lead genetic variants associated with personality, including 823 novel variants. Common genetic variants explain 4.8%-9.3% of the variance in each trait, and 10.5%-16.2% accounting for measurement unreliability. Genetic effects on personality are highly consistent across geography, reporter (self vs. close other), age group, and measurement instrument, and we find minimal spousal assortment for personality in recent history. In stark contrast to many other social and behavioral traits, within-family GWAS and polygenic index analyses indicate little to no shared environmental confounding in genetic associations with personality. Polygenic prediction, genetic correlation, and Mendelian randomization analyses indicate that personality genetics have widespread, potentially causal associations with a wide range of consequential behaviors and life outcomes. The genetic architecture of personality is robust and fundamental to being a human.

Measures of intelligence predict socio-political attitudes and behaviors, such as liberalism, religiosity, and voter turnout. Little, however, is known about which cognitive abilities are responsible for these relationships. Employing several cohorts from the Minnesota Center for Twin and Family Research, we test the predictive performance of different broad abilities. Using multiple regression to compare verbal and performance IQ from Wechsler intelligence tests, we find verbal IQ more strongly predicts voter turnout, civic engagement, traditionalism, and measures of ideology. On average, the correlation between verbal IQ and our socio-political attitudes is twice as large as that of performance IQ. The same pattern appears after controlling for education and after performing the analysis within sibling pairs. This implies that the relationship cannot be entirely mediated through education, nor entirely confounded by upbringing. Positive and negative controls are employed to test the validity of our methodology. Importantly, we find verbal and performance IQ to be equally predictive of the ICAR-16, a distinct measure of general intelligence. The results imply that variation in cognitive abilities, which are orthogonal to general intelligence, influence socio-political attitudes and behaviors. The role of verbal ability in influencing attitudes may help to explain the ideological leanings of specific occupations. Its association with turnout and civic engagement suggests that those with a verbal tilt may have greater influence over politics and society.

Intelligence is correlated with a range of left-wing and liberal political beliefs. This may suggest intelligence directly alters our political views. Alternatively, the association may be confounded or mediated by socioeconomic and environmental factors. We studied the effect of intelligence within a sample of over 300 biological and adoptive families, using both measured IQ and polygenic scores for cognitive performance and educational attainment. We found both IQ and polygenic scores significantly predicted all six of our political scales. Polygenic scores predicted social liberalism and lower authoritarianism, within-families. Intelligence was able to significantly predict social liberalism and lower authoritarianism, within families, even after controlling for socioeconomic variables. Our findings may provide the strongest causal inference to date of intelligence directly affecting political beliefs.

Saving disposition, the tendency to save rather than consume, has been found to be associated with economic outcomes. People lacking the disposition to save are more likely to experience financial distress. This association could be driven by other economic factors, behavioral traits, or even genetic effects. Using a sample of 3,920 American twins, we develop scales to measure saving disposition and financial distress. We find genetic influences on both traits, but also a large effect of the rearing family environment on saving disposition. We estimate that 44% of the covariance between the two traits is due to genetic effects. Saving disposition remains strongly associated with lower financial distress, even after controlling for family income, cognitive ability, and personality traits. The association persists within families and monozygotic twin pairs; the twin who saves more tends to be the twin who experiences less financial distress. This result suggest that there is a direct association between saving disposition and financial distress, although the direction of causation remains unclear.

Currently, no pharmacological therapies treat skeletal muscle insulin resistance in pathological conditions such as type 2 diabetes, age-associated diseases, and cancer. Therefore, there is an unmet need to identify the molecular mechanisms ...The molecular events governing skeletal muscle glucose uptake have pharmacological potential for managing insulin resistance in conditions such as obesity, diabetes, and cancer. With no current pharmacological treatments to target skeletal muscle insulin ...

The construct validity of group factor models of personality, which are typically derived from factor analysis of questionnaire items, relies on the ability of each factor to predict meaningful and differentiated real-world outcomes. In a sample of 481 participants, we used the Big Five Aspect Scales (BFAS) personality questionnaire, two laboratory-measured reaction time (RT) tasks, and a short-form test of cognitive ability (ICAR-16) to test the hypothesis that the Intellect and Openness aspects of Big Five Openness to Experience differentially correlate with reaction time moments. We found that higher scores on the Intellect aspect significantly correlate with faster and less variable response times, while no such association is observed for the Openness aspect. Further, we found that this advantage lies solely in the decisional, but not perceptual, stage of information processing; no other Big Five aspect showed a similar pattern of results. In sum, these findings represent the largest and most comprehensive study to date on personality factors and reaction time, and the first to demonstrate a mechanistic validation of BFAS Intellect through a differential pattern of associations with RT and Big Five personality aspects.

We applied structural equation modeling to genome-wide association studies (GWAS) of the items in a Neuroticism questionnaire. We categorized significant genetic variants as acting either through the Neuroticism general factor, through other factors measured by the questionnaire, or through paths independent of any factor. Bioinformatic analysis showed that the genetic variants associated with the Neuroticism general factor tend to lie near or within genes expressed in the brain. Enriched gene sets suggest behaviors in mice indicative of fear and anxiety. Psychologists have long asked whether psychometric common factors are merely a convenient summary of correlated variables or causal enti-ties with a partial biological basis, and our results provide some support for the latter interpretation. Further research is needed to determine the extent to which causes resem-bling common factors operate alongside other mechanisms to generate the correlational structure of personality.

We extend a standard model of parental investment and intergenerational mobility to include a fully specified genetic analysis of skill transmission. The model’s predictions differ substantially from the standard model’s. The coefficient of intergenerational income elasticity (IGE) may be larger than that in the standard model and depends on the distribution of the genotype. The distribution of genetic endowments may be stratified according to income. The model is tested on data, including genetic information, of twins and their parents, estimating how IGE is affected by genetic factors and how environment and genes interact. The effect of intelligence is substantially stronger than that of other traits.

We applied structural equation modeling to conduct a genome-wide association study (GWAS) of the general factor measured by a neuroticism questionnaire administered to ∼ 380,000 participants in the UK Biobank. We categorized significant genetic variants as acting either through the neuroticism general factor, through other factors measured by the questionnaire, or through paths independent of any factor. Regardless of this categorization, however, significant variants tended to show concordant associations with all items. Bioinformatic analysis showed that the variants associated with the neuroticism general factor disproportionately lie near or within genes expressed in the brain. Enriched gene sets pointed to an underlying biological basis associated with brain development, synaptic function, and behaviors in mice indicative of fear and anxiety. Psychologists have long asked whether psychometric common factors are merely a convenient summary of correlated variables or reflect coherent causal entities with a partial biological basis, and our results provide some support for the latter interpretation. Further research is needed to determine the extent to which causes resembling common factors operate alongside other mechanisms to generate the correlational structure of personality.

In a sample of Korean adoptees who have been quasi-randomly assigned to US adoptive families and who have been genotyped, we examine the influences and interplay of genetics (“nature”) and shared family environment (“nurture”) on a suite of outcomes. We use molecular genetic data to construct polygenic indices (PGIs) that partially predict the outcomes and examine the effects of the PGIs as well as those of a rich set of family variables. We also compare the resemblance of adoptive and biological siblings to decompose outcome variation into shares due to nature and nurture. We find that both nature and nurture causally affect most outcomes and that the influence of the PGIs tends to be of a similar magnitude to that of the observed family variables. Nurture appears particularly important for education, income, and nicotine usage, while nature has a particularly strong influence on GPA, soft skills, cognitive performance, BMI, and height. Nurture effects on education and smoking are partly traceable to rearing parents’ genetics. We investigate interactive effects and obtain suggestive evidence that family socioeconomic status and genetic propensity for educational attainment may be substitutes in the human capital production function for cognitive skills.

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57.