Background: Cannabis use is associated with outcomes like income, legal problems, and psychopathology. This finding rests largely on correlational research designs, which rely at best on statistical controls for confounding. Here, we control for unmeasured confounders using a longitudinal study of twins. Method: In a sample of 4,078 American adult twins first assessed decades ago, we used cotwin control mixed effects models to evaluate the effect of lifetime average frequency of cannabis consumption measured on substance use, psychiatric, and psychosocial outcomes. Results: On average, participants had a lifetime cannabis frequency of about one to two times per month, across adolescence and adulthood. As expected, in individual-level analyses, cannabis use was significantly associated with almost all outcomes in the expected directions. However, when comparing each twin to their cotwin, which inherently controls for shared genes and environments, we observed within-pair differences consistent with possible causality in three of the 22 assessed outcomes: cannabis use disorder symptoms (βW-Pooled = .15, SE = .02, p = 1.7 × 10−22), frequency of tobacco use (βW-Pooled = .06, SE = .01, p = 1.2 × 10−5), and illicit drug involvement (βW-Pooled = .06, SE = .02, p = 1.2 × 10−4). Covariate specification curve analyses indicated that within-pair effects on tobacco and illicit drug use, but not cannabis use disorder, attenuated substantially when covarying for lifetime alcohol and tobacco use. Conclusions: The cotwin control results suggest that more frequent cannabis use causes small increases in cannabis use disorder symptoms, approximately 1.3 symptoms when going from a once-a-year use to daily use. For other outcomes, our results are more consistent with familial confounding, at least in this community population of twins. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Job performance has been recognized as multifaceted, with multiple models presented in the literature. Rotundo and Sackett (2002) provided a succinct model of job performance as consisting of task ...

Understanding eating-pathology development may enable meaningful prescriptions for its prevention. Here, we identified common trajectories of eating-pathology development and the personality factors associated with these trajectories. Participants were 760 female twins from the Minnesota Twin Family Study who reported on eating pathology at approximate ages 11, 14, 18, 20, 24, and 29. Parents reported on twins’ personality characteristics at age 11, and twins completed self-report personality questionnaires at ages 14 and 18. Latent class growth analysis identified two distinct trajectories for total eating pathology, binge eating, and weight preoccupation and three distinct trajectories for body dissatisfaction. Girls with more pathological trajectories already showed elevated eating pathology at age 11. These subgroups of high-risk girls self-reported greater proneness to anxiety, stress, and alienation, and less sociable personality styles. Prevention efforts may be enhanced by using self-reported personality traits to identify girls at high risk for eating pathology.

STUDY QUESTION: Which genetic factors regulate female propensity for giving birth to spontaneous dizygotic (DZ) twins? SUMMARY ANSWER: We identified four new loci, GNRH1, FSHR, ZFPM1, and IPO8, in addition to previously identified loci, FSHB and SMAD3.

Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury1–4. These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries5. Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction. A multi-ancestry meta-regression study analyses diverse genome-wide association studies and genome loci associated with tobacco and alcohol use.

The University of Minnesota has played an important role in the resurgence and eventual mainstreaming of human behavioral genetics in psychology and psychiatry. We describe this history in the context of three major movements in behavioral genetics: (1) radical eugenics in the early 20th century, (2) resurgence of human behavioral genetics in the 1960s, largely using twin and adoption designs to obtain more precise estimates of genetic and environmental influences on individual differences in behavior; and (3) use of measured genotypes to understand behavior. University of Minnesota scientists made significant contributions especially in (2) and (3) in the domains of cognitive ability, drug abuse and mental health, and endophenotypes. These contributions are illustrated through a historical perspective of major figures and events in behavioral genetics. Human behavioral-genetic facts, theory and methodologies have become integral and mainstream in psychology, psychiatry and related behavioral disciplines. It was not always this way. Here, we outline major milestones in the history of behavioral genetics, and then describe how activities at the University of Minnesota contributed to these events. While our focus on Minnesota by necessity does not detail the many important contributions from scientists at other institutions, our goal is to present a focused history of a single institution and tradition of research, and perhaps encourage those at other institutions to do the same. Behavioral-genetic ideas are traceable to animal breeding and domestication, although the practitioners were not completely aware of the implications of the domestication process. The beginnings of the field of human behavioral genetics as a formal scientific discipline are often attributed to Francis Galton, a broadly influential figure in the history of psychology who, among many other innovations, proposed family, twin and adoption studies to parse genetic and environmental origins of behavioral attributes. Galton increasingly turned his attention to eugenics in the early 20th century, having coined the term 'well-born' in 1883. These movements were embraced by progressive writers and politicians as a means to improve the common good, at the expense of some individuals, often through forced sterilization. Eugenics laws in Western countries, including the United States, were used as models by Nazi Germany, which notoriously took them to more terrifying extremes. The postwar vilification of eugenics and, by extension, behavioral genetics, chilled genetic research on behavior for decades. Psychology and psychiatry, bereft of behavioral-genetic thought, drifted to radical environmental explanations of behavior reminiscent of the tabula rasa, including schizophreno-genic mothers causing schizophrenia in their offspring. The resurgence of behavioral-genetic research began in earnest in the 1960s when graduate training programs began emerging in US institutions, including the University of Colorado Boulder, University of Texas at Austin and the University of Minnesota. During the next four decades, twin and adoption studies routinely found that psychological traits and psychopathology were heritable, and behavioral geneticists went to lengths to test assumptions and refine their study designs to meet the many prominent critics of such findings. Overlapping this era of twin and adoption studies, Gusella et al. (1983) discovered linkage between the short arm of chromosome 4 and Huntington's chorea in 1983, ushering in a new era of excitement in gene mapping and biological explanations of complex behaviors. Linkage studies of other behavioral disorders soon followed , with limited success for complex traits. The Human Genome Project, completed in 2003, paved the way for the current technological revolution in behavioral genetics: the use of genome-wide DNA markers. Genomewide association studies of common variants have been conducted at large scales now for over a decade, and whole-genome sequencing studies of the full allelic spectrum are following. These data are being combined with new analytical technologies not just to map genes to phenotypes, but to complement and extend traditional family studies such as twin and adoption designs. The University of Minnesota and its faculty and staff have significantly contributed along the way, especially from the 1960s onward. Here, we outline some of these contributions. Early History at Minnesota: The Role of Psychology The beginning of behavioral-genetic research and scholarship at Minnesota is not simple to trace. From 1890 to 1899, psychology

<p>While prior research has demonstrated a relationship between sleep and cognitive performance, how sleep relates to underlying genetic and environmental etiologies contributing to cognitive functioning, regardless of the level of cognitive function, is unclear. The present study assessed whether the importance of genetic and environmental contributions to cognition vary depending on an individual’s aging-related sleep characteristics. The large sample consisted of twins from six studies within the Interplay of Genes and Environment across Multiple Studies (IGEMS) consortium spanning mid- to late-life (Average age (Mage)=57.6, range= 27 to 91 years, N=7052, Female=43.70%, 1525 complete monozygotic (MZ) pairs, 2001 complete dizygotic (DZ) pairs). Quantitative genetic twin models considered sleep duration as a primary moderator of genetic and environmental contributions to cognitive performance in four cognitive abilities (Semantic Fluency, Spatial-Visual Reasoning, Processing Speed, and Episodic Memory), while accounting for age moderation. Results suggested genetic and both shared and nonshared environmental contributions for Semantic Fluency and genetic and shared environmental contributions for Episodic Memory vary by sleep duration, while no significant moderation was observed for Spatial-Visual Reasoning or Processing Speed. Results for Semantic Fluency and Episodic Memory illustrated patterns of higher genetic influences on cognitive function at shorter sleep durations (i.e., 4 hours) and higher shared environmental contributions to cognitive function at longer sleep durations (i.e., 10 hours). Overall, these findings may align with associations of upregulation of neuroinflammatory processes and ineffective beta-amyloid clearance in short sleep contexts and common reporting of mental fatigue in long sleep contexts, both associated with poorer cognitive functioning.</p>

Given the well-documented importance of counterproductiveworkplace behavior and organizational citizenship behavior (together nontask performance), it is important to clarify the degree to which these behaviors are attributable to organizational climate versus preexisting individual differences. Such clarification informs where these behaviors stem from, and consequently has practical implications for organizations (e.g., guiding prioritization of selection criteria). We investigated familial resemblance for nontask performance among twins, nontwin and adoptive siblings, parents and offspring, and midlife and late-life couples drawn from two, large-scale studies: the Minnesota Twin Family Study and the Sibling Interaction Behavior Study. Similarity among family members’ (e.g., parents–offspring, siblings) engagement in nontask performance was assessed to estimate the degree to which preexisting individual differences (i.e., genetic variability) and the environment (i.e., environmentality) accounted for variation in counterproductive and citizenship behavior. We found that degree of familial resemblance for nontask performance increased with increasing genetic relationship. Nonetheless, genetically identical individuals correlated only moderately in their workplace behavior (r. .29–.40), highlighting the importance of environmental differences. Notably, familymemberswere more similar in their counterproductive than citizenship behavior, suggesting citizenship behavior is comparatively more environmentally influenced. Spouse/partner similarity for nontask behavior was modest and did not vary between midlife and late-life couples, suggesting spousal influence on nontask performance is limited. These findings offer insight to organizations regarding the degree of nature (individual differences) and nurture (including organizational factors) influences on nontask performance, which has implications for the selection of interventions (e.g., relative value of applicant selection or incumbent interventions).

Aims: To estimate the effect of recreational legalization on cannabis use frequency and sources of variance across legal environments. Design: Longitudinal discordant twin and gene–environment interaction models in twins recruited from birth records and assessed prospectively. Setting: The United States, including states with different recreational cannabis policies before and after 2014, when recreational cannabis was first legalized. Participants: Two longitudinal, prospectively assessed samples of American twins aged 24–47 (n = 1425 in legal states, n = 1996 in illegal states), including 111 monozygotic pairs discordant for residence. Measurements: Current cannabis use frequency (measured continuously and ordinally) was the primary outcome, and the predictor was recreational status of cannabis (legal/illegal) in the participant’s state of residence at the time of assessment. Covariates include age, sex and cannabis use frequency prior to 2014. Findings: Accounting for pre-2014 use, residents of legal states used cannabis more frequently than residents of illegal states (b = 0.21, P = 8.08 × 10−5). Comparing 111 pairs of monozygotic twins discordant for residence confirmed the effect (b = 0.18, P = 0.014). There was inconclusive evidence for genetic influences on cannabis use frequency that were specific to the legal environment [χ2 = 2.9 × 10−9, degrees of freedom (d.f.) = 1, P > 0.999]. Existing genetic influences were moderated by the legal environment, as the genetic correlation between marijuana use before and after legalization was lower in states that legalized (rgenetic = 0.24) compared with states that did not (rgenetic = 0.78, Pdifference = 0.016). Conclusions: In the United States, there appears to be a ~ 20% average increase in cannabis use frequency attributable to recreational legalization, consistent across increasingly rigorous designs. In addition, the heritability of cannabis use frequency appears to be moderated by legalization.

Twin studies demonstrate significant environmental influences and a lack of genetic effects on disordered eating before puberty in girls. However, genetic factors could act indirectly through passive gene–environment correlations (rGE; correlations between parents’ genes and an environment shaped by those genes) that inflate environmental (but not genetic) estimates. The only study to explore passive rGE did not find significant effects, but the full range of parental phenotypes (e.g., internalizing symptoms) that could impact daughters’ disordered eating was not examined. We addressed this gap by exploring whether parents’ internalizing symptoms (e.g., anxiety, depressive symptoms) contribute to daughters’ eating pathology through passive rGE. Participants were female twin pairs (aged 8–14 years; M = 10.44) in pre-early puberty and their biological parents (n = 279 families) from the Michigan State University Twin Registry. Nuclear twin family models explored passive rGE for parents’ internalizing traits/symptoms and twins’ overall eating disorder symptoms. No evidence for passive rGE was found. Instead, environmental factors that create similarities between co-twins (but not with their parents) and unique environmental factors were important. In pre-early puberty, genetic factors do not influence daughters’ disordered eating, even indirectly through passive rGE. Future research should explore sibling-specific and unique environmental factors during this critical developmental period.

Observational studies have repeatedly linked cannabis use and increased risk of psychosis. We sought to clarify whether this association reflects a causal effect of cannabis exposure or residual confounding. We analyzed data from two cohorts of twins who completed repeated, prospective measures of cannabis use (N = 1544) and cannabis use disorder symptoms (N = 1458) in adolescence and a dimensional measure of psychosis-proneness (the Personality Inventory for DSM–5 Psychoticism scale) in adulthood. Twins also provided molecular genetic data, which were used to estimate polygenic risk of schizophrenia. Both cumulative adolescent cannabis use and use disorder were associated with higher Psychoticism scores in adulthood. However, we found no evidence of an effect of cannabis on Psychoticism or any of its facets in co-twin control models that compared the greater-cannabis-using twin to the lesser-using co-twin. We also observed no evidence of a differential effect of cannabis on Psychoticism by polygenic risk of schizophrenia. Although cannabis use and disorder are consistently associated with increased risk of psychosis, the present results suggest this association is likely attributable to familial confounds rather than a causal effect of cannabis exposure. Efforts to reduce the prevalence and burden of psychotic illnesses thus may benefit from greater focus on other therapeutic targets. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

<p>We examined associations between common psychiatric disorders and fecundity in a population-based cohort of 1,252 twins prospectively assessed from adolescence into adulthood. Major depressive disorder, anxiety disorders, and alcohol use disorders were associated with lower likelihood of having children and having fewer children. Survival analyses yielded similar results accounting for timing and recurrence. Although both early- and adult-onset psychiatric disorders were associated with decreased fecundity, early-onset major depressive disorder, anxiety disorders (among boys), and alcohol use disorders (among girls) were associated with greater likelihood of having a child during adolescence. Among twin pairs discordant for psychiatric disorders (i.e., one twin affected and one twin unaffected by major depressive disorder, anxiety disorders, or alcohol use disorders), twins affected by anxiety and alcohol use disorders but not major depressive disorder were less likely to have children than their unaffected co-twins. However, unaffected twins with an affected co-twin were no more likely to have children than twins from unaffected twin pairs, inconsistent with the balancing-selection hypothesis that increased fecundity in unaffected relatives accounts for persistence of psychiatric disorders.</p>

Objective: Prior literature indicates that nontraditional attitudes are linked to higher intelligence. However, such attitudes in adolescence often accompany counter-normative, delinquent-type behaviors, which are themselves negatively linked with intelligence. This points to the possibility of suppression in the relationship between intelligence and nontraditional attitudes. Method: We analyzed a large community sample of 17 year olds (N = 3330) with data on intelligence, nontraditional attitudes, and a diverse collection of self- and teacher-reported counter-normative behaviors. Developmental questions for these relationships were examined through cross-sectional comparisons between the adolescents and their parents as well as longitudinal analysis of the adolescent sample across emerging adulthood. Results: Youth who endorsed nontraditional attitudes had lower school grades, earlier age at first sex, heavier substance use, and were perceived as more oppositional by their teachers. Each of these problem behaviors was inversely related to intelligence. Accordingly, the positive correlation between nontraditional attitudes and intelligence was much weaker in adolescents as compared to their middle-aged parents. Longitudinal analyses revealed that the association between nontraditional attitudes and intelligence strengthens in early adulthood. Conclusions: Associations between intelligence and sociopolitical attitudes can be obscured even by seemingly distal psychological characteristics.

Observational studies have linked cannabis use to an array of negative outcomes, including psychiatric symptoms, cognitive impairment, and educational and occupational underachievement. These associations are particularly strong when cannabis use occurs in adolescence. Nevertheless, causality remains unclear. The purpose of the present study was thus to examine associations between prospectively assessed adolescent cannabis use and young-adult outcomes (psychiatric, cognitive, and socioeconomic) in three longitudinal studies of twins (n = 3,762). Twins reporting greater cumulative cannabis use in adolescence reported higher levels of psychopathology as well as poorer socioeconomic outcomes in young adulthood. However, cannabis use remained associated only with socioeconomic outcomes (i.e., educational attainment, occupational status, and income) in monozygotic-cotwin control analyses, which account fully for shared genetic and environmental confounding. Follow-up analyses examining associations between twin differences in adolescent cannabis use and longitudinal change in academic functioning during the middle- and high-school years provided a possible mechanism for these associations, indicating that greater cannabis use during this period was associated with decreases in grade point average and academic motivation as well as increases in academic problem behavior and school disciplinary problems. Our findings thus suggest that cannabis use in adolescence has potentially causal, deleterious effects on adolescent academic functioning and young-adult socioeconomic outcomes despite little evidence suggesting a strong, causal influence on adult mental health or cognitive ability.

Parent-child similarity is a function of genetic and environmental transmission. In addition, genetic effects not transmitted to offspring may drive parental behavior, thereby affecting the rearing environment of the child. Measuring genetic proclivity directly, through polygenic risk scores (PRSs), provides a way to test for the effect of nontransmitted parental genotype, on offspring outcome, termed a genetic nurture effect-in other words, if and how parental genomes might affect their children through the environment. The current study used polygenic risk scores for smoking initiation, cigarettes per day, and drinks per week to predict substance use in a sample of 3,008 twins, assessed prospectively from age 17-29, and their parents, from the Minnesota Center for Twin and Family Research. Mixed-effects models were used to test for a genetic nurture effect whereby parental PRSs predict offspring tobacco and alcohol use after statistically adjusting for offspring's own PRS. Parental smoking initiation PRS predicted offspring cigarettes per day at age 24 (β = .103, 95% CI [.03, .17]) and alcohol use at age 17 (β = .091, 95% CI [.04, .14]) independent of shared genetics. There was also a suggestive independent association between the parent PRS and offspring smoking at age 17 (β = .096; 95% CI [.02, .17]). Mediation analyses provided some evidence for environmental effects of parental smoking, alcohol use, and family socioeconomic status. These findings, and more broadly the molecular genetic method used, have implications on the identification of environmental effects on developmental outcomes such as substance use. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Genetic factors explain a major proportion of human height variation, but differences in mean stature have also been found between socio-economic categories suggesting a possible effect of environment. By utilizing a classical twin design which allows decomposing the variation of height into genetic and environmental components, we tested the hypothesis that environmental variation in height is greater in offspring of lower educated parents. Twin data from 29 cohorts including 65,978 complete twin pairs with information on height at ages 1 to 69 years and on parental education were pooled allowing the analyses at different ages and in three geographic-cultural regions (Europe, North America and Australia, and East Asia). Parental education mostly showed a positive association with offspring height, with significant associations in mid-childhood and from adolescence onwards. In variance decomposition modeling, the genetic and environmental variance components of height did not show a consistent relation to parental education. A random-effects meta-regression analysis of the aggregate-level data showed a trend towards greater shared environmental variation of height in low parental education families. In conclusion, in our very large dataset from twin cohorts around the globe, these results provide only weak evidence for the study hypothesis.

We investigated the heritability of educational attainment and how it differed between birth cohorts and cultural–geographic regions. A classical twin design was applied to pooled data from 28 cohorts representing 16 countries and including 193,518 twins with information on educational attainment at 25 years of age or older. Genetic factors explained the major part of individual differences in educational attainment (heritability: a2 = 0.43; 0.41–0.44), but also environmental variation shared by co-twins was substantial (c2 = 0.31; 0.30–0.33). The proportions of educational variation explained by genetic and shared environmental factors did not differ between Europe, North America and Australia, and East Asia. When restricted to twins 30 years or older to confirm finalized education, the heritability was higher in the older cohorts born in 1900–1949 (a2 = 0.44; 0.41–0.46) than in the later cohorts born in 1950–1989 (a2 = 0.38; 0.36–0.40), with a corresponding lower influence of common environmental factors (c2 = 0.31; 0.29–0.33 and c2 = 0.34; 0.32–0.36, respectively). In conclusion, both genetic and environmental factors shared by co-twins have an important influence on individual differences in educational attainment. The effect of genetic factors on educational attainment has decreased from the cohorts born before to those born after the 1950s.

Genome-wide association studies (GWASs) are a popular tool for detecting association between genetic variants or single nucleotide polymorphisms (SNPs) and complex traits. Family data introduce complexity due to the non-independence of the family members. Methods for non-independent data are well established, but when the GWAS contains distinct family types, explicit modeling of between-family-type differences in the dependence structure comes at the cost of significantly increased computational burden. The situation is exacerbated with binary traits. In this paper, we perform several simulation studies to compare multiple candidate methods to perform single SNP association analysis with binary traits. We consider generalized estimating equations (GEE), generalized linear mixed models (GLMMs), or generalized least square (GLS) approaches. We study the influence of different working correlation structures for GEE on the GWAS findings and also the performance of different analysis method(s) to conduct a GWAS with binary trait data in families. We discuss the merits of each approach with attention to their applicability in a GWAS. We also compare the performances of the methods on the alcoholism data from the Minnesota Center for Twin and Family Research (MCTFR) study.