Genome-wide association study meta-analysis of dizygotic twinning illuminates genetic regulation of female fecundity.

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. WHAT IS KNOWN ALREADY: The propensity to give birth to DZ twins runs in families. Earlier, we reported that FSHB and SMAD3 as associated with DZ twinning and female fertility measures. STUDY DESIGN, SIZE, DURATION: We conducted a genome-wide association meta-analysis (GWAMA) of mothers of spontaneous dizygotic (DZ) twins (8265 cases, 264 567 controls) and of independent DZ twin offspring (26 252 cases, 417 433 controls). PARTICIPANTS/MATERIALS, SETTING, METHODS: Over 700 000 mothers of DZ twins, twin individuals and singletons from large cohorts in Australia/New Zealand, Europe, and the USA were carefully screened to exclude twins born after use of ARTs. Genetic association analyses by cohort were followed by meta-analysis, phenome wide association studies (PheWAS), in silico and in vivo annotations, and Zebrafish functional validation. MAIN RESULTS AND THE ROLE OF CHANCE: This study enlarges the sample size considerably from previous efforts, finding four genome-wide significant loci, including two novel signals and a further two novel genes that are implicated by gene level enrichment analyses. The novel loci, GNRH1 and FSHR, have well-established roles in female reproduction whereas ZFPM1 and IPO8 have not previously been implicated in female fertility. We found significant genetic correlations with multiple aspects of female reproduction and body size as well as evidence for significant selection against DZ twinning during human evolution. The 26 top single nucleotide polymorphisms (SNPs) from our GWAMA in European-origin participants weakly predicted the crude twinning rates in 47 non-European populations (r = 0.23 between risk score and population prevalence, s.e. 0.11, 1-tail P = 0.058) indicating that genome-wide association studies (GWAS) are needed in African and Asian populations to explore the causes of their respectively high and low DZ twinning rates. In vivo functional tests in zebrafish for IPO8 validated its essential role in female, but not male, fertility. In most regions, risk SNPs linked to known expression quantitative trait loci (eQTLs). Top SNPs were associated with in vivo reproductive hormone levels with the top pathways including hormone ligand binding receptors and the ovulation cycle. LARGE SCALE DATA: The full DZT GWAS summary statistics will made available after publication through the GWAS catalog (https://www.ebi.ac.uk/gwas/). LIMITATIONS, REASONS FOR CAUTION: Our study only included European ancestry cohorts. Inclusion of data from Africa (with the highest twining rate) and Asia (with the lowest rate) would illuminate further the biology of twinning and female fertility. WIDER IMPLICATIONS OF THE FINDINGS: About one in 40 babies born in the world is a twin and there is much speculation on why twinning runs in families. We hope our results will inform investigations of ovarian response in new and existing ARTs and the causes of female infertility. STUDY FUNDING/COMPETING INTEREST(S): Support for the Netherlands Twin Register came from the Netherlands Organization for Scientific Research (NWO) and The Netherlands Organization for Health Research and Development (ZonMW) grants, 904-61-193, 480-04-004, 400-05-717, Addiction-31160008, 911-09-032, Biobanking and Biomolecular Resources Research Infrastructure (BBMRI.NL, 184.021.007), Royal Netherlands Academy of Science Professor Award (PAH/6635) to DIB, European Research Council (ERC-230374), Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06), the Avera Institute, Sioux Falls, South Dakota (USA) and the National Institutes of Health (NIH R01 HD042157-01A1) and the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health and Grand Opportunity grants 1RC2 MH089951. The QIMR Berghofer Medical Research Institute (QIMR) study was supported by grants from the National Health and Medical Research Council (NHMRC) of Australia (241944, 339462, 389927, 389875, 389891, 389892, 389938, 443036, 442915, 442981, 496610, 496739, 552485, 552498, 1050208, 1075175). L.Y. is funded by Australian Research Council (Grant number DE200100425). The Minnesota Center for Twin and Family Research (MCTFR) was supported in part by USPHS Grants from the National Institute on Alcohol Abuse and Alcoholism (AA09367 and AA11886) and the National Institute on Drug Abuse (DA05147, DA13240, and DA024417). The Women's Genome Health Study (WGHS) was funded by the National Heart, Lung, and Blood Institute (HL043851 and HL080467) and the National Cancer Institute (CA047988 and UM1CA182913), with support for genotyping provided by Amgen. Data collection in the Finnish Twin Registry has been supported by the Wellcome Trust Sanger Institute, the Broad Institute, ENGAGE-European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement number 201413, National Institute of Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145, AA-09203, AA15416, and K02AA018755) and the Academy of Finland (grants 100499, 205585, 118555, 141054, 264146, 308248, 312073 and 336823 to J. Kaprio). TwinsUK is funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation (CDRF), Zoe Ltd and the National Institute for Health Research (NIHR) Clinical Research Network (CRN) and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. For NESDA, funding was obtained from the Netherlands Organization for Scientific Research (Geestkracht program grant 10000-1002), the Center for Medical Systems Biology (CSMB, NVVO Genomics), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL), VU University's Institutes for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam, University Medical Center Groningen, Leiden University Medical Center, National Institutes of Health (NIH, ROI D0042157-01A, MH081802, Grand Opportunity grants 1 RC2 Ml-1089951 and IRC2 MH089995). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health. Computing was supported by BiG Grid, the Dutch e-Science Grid, which is financially supported by NWO. Work in the Del Bene lab was supported by the Programme Investissements d'Avenir IHU FOReSIGHT (ANR-18-IAHU-01). C.R. was supported by an EU Horizon 2020 Marie Sklodowska-Curie Action fellowship (H2020-MSCA-IF-2014 #661527). H.S. and K.S. are employees of deCODE Genetics/Amgen. The other authors declare no competing financial interests. TRIAL REGISTRATION NUMBER: N/A.

Shifting goalposts: widening discrepancies between girls' actual and ideal bodies predict disordered eating from preadolescence to adulthood.

BACKGROUND: Little is known regarding how disordered eating (DE) relates to perceived actual body size, ideal body size, and their discrepancy. This study examined changes in perceived actual body size, ideal body size, and actual-ideal discrepancies over time, and their relationship with subsequent DE. METHODS: Participants were 759 female twins from the Minnesota Twin Family Study who reported on body image and DE every three to five years between approximately ages 11 to 29. We used multilevel modeling to examine developmental trajectories of body mass index (BMI) and Body Rating Scale Actual, Ideal, and Actual-Ideal discrepancy scores and compared the degree to which BMI, BRS body size perceptions, and body dissatisfaction predicted DE behaviors and attitudes over time. Participants were treated as singletons in analyses. RESULTS: Perceived Actual body sizes and BMIs increased from age 10 to 33, whereas Ideal body sizes remained largely stable across time, resulting in growing Actual-Ideal discrepancies. Body size perceptions and Actual-Ideal discrepancies predicted subsequent DE behaviors and attitudes more strongly than did body dissatisfaction as measured by self-report questionnaires. CONCLUSIONS: This research advances understanding of how female body size perceptions and ideals change across development and highlights their relationship with subsequent DE.

Associations between adolescent cannabis use and young-adult functioning in three longitudinal twin studies.

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.

Testing the consequences of alcohol, cannabis, and nicotine use on hippocampal volume: a quasi-experimental cotwin control analysis of young adult twins.

BACKGROUND: Alcohol, cannabis, and nicotine use are highly comorbid and alarmingly prevalent in young adults. The hippocampus may be particularly sensitive to substance exposure. This remains largely untested in humans and familial risk may confound exposure effects. We extend prior work on alcohol and hippocampal volume in women by testing common and unique substance use effects and the potential moderating role of sex on hippocampal volume during emerging adulthood. A quasi-experimental cotwin control (CTC) design was used to separate familial risk from exposure consequences. METHODS: In a population-based sample of 435 24-year-old same-sex twins (58% women), dimensional measures (e.g. frequency, amount) of alcohol, cannabis, and nicotine use across emerging adulthood were assessed. Hippocampal volume was assessed using MRI. RESULTS: Greater substance use was significantly associated with lower hippocampal volume for women but not men. The same pattern was observed for alcohol, cannabis, and nicotine. CTC analyses provided evidence that hippocampal effects likely reflected familial risk and the consequence of substance use in general and alcohol and nicotine in particular; cannabis effects were in the expected direction but not significant. Within-pair mediation analyses suggested that the effect of alcohol use on the hippocampus may reflect, in part, comorbid nicotine use. CONCLUSIONS: The observed hippocampal volume deviations in women likely reflected substance-related premorbid familial risk and the consequences of smoking and, to a lesser degree, drinking. Findings contribute to a growing body of work suggesting heightened risk among women toward experiencing deleterious effects of substance exposure on the still-developing young adult hippocampus.

Associations between polygenic risk of substance use and use disorder and alcohol, cannabis, and nicotine use in adolescence and young adulthood in a longitudinal twin study.

BACKGROUND: Recent well-powered genome-wide association studies have enhanced prediction of substance use outcomes via polygenic scores (PGSs). Here, we test (1) whether these scores contribute to prediction over-and-above family history, (2) the extent to which PGS prediction reflects inherited genetic variation v. demography (population stratification and assortative mating) and indirect genetic effects of parents (genetic nurture), and (3) whether PGS prediction is mediated by behavioral disinhibition prior to substance use onset. METHODS: PGSs for alcohol, cannabis, and nicotine use/use disorder were calculated for Minnesota Twin Family Study participants (N = 2483, 1565 monozygotic/918 dizygotic). Twins' parents were assessed for histories of substance use disorder. Twins were assessed for behavioral disinhibition at age 11 and substance use from ages 14 to 24. PGS prediction of substance use was examined using linear mixed-effects, within-twin pair, and structural equation models. RESULTS: Nearly all PGS measures were associated with multiple types of substance use independently of family history. However, most within-pair PGS prediction estimates were substantially smaller than the corresponding between-pair estimates, suggesting that prediction is driven in part by demography and indirect genetic effects of parents. Path analyses indicated the effects of both PGSs and family history on substance use were mediated via disinhibition in preadolescence. CONCLUSIONS: PGSs capturing risk of substance use and use disorder can be combined with family history measures to augment prediction of substance use outcomes. Results highlight indirect sources of genetic associations and preadolescent elevations in behavioral disinhibition as two routes through which these scores may relate to substance use.

Genetic and Environmental Variation in Continuous Phenotypes in the ABCD Study®.

Twin studies yield valuable insights into the sources of variation, covariation and causation in human traits. The ABCD Study® (abcdstudy.org) was designed to take advantage of four universities known for their twin research, neuroimaging, population-based sampling, and expertise in genetic epidemiology so that representative twin studies could be performed. In this paper we use the twin data to: (i) provide initial estimates of heritability for the wide range of phenotypes assessed in the ABCD Study using a consistent direct variance estimation approach, assuring that both data and methodology are sound; and (ii) provide an online resource for researchers that can serve as a reference point for future behavior genetic studies of this publicly available dataset. Data were analyzed from 772 pairs of twins aged 9-10 years at study inception, with zygosity determined using genotypic data, recruited and assessed at four twin hub sites. The online tool provides twin correlations and both standardized and unstandardized estimates of additive genetic, and environmental variation for 14,500 continuously distributed phenotypic features, including: structural and functional neuroimaging, neurocognition, personality, psychopathology, substance use propensity, physical, and environmental trait variables. The estimates were obtained using an unconstrained variance approach, so they can be incorporated directly into meta-analyses without upwardly biasing aggregate estimates. The results indicated broad consistency with prior literature where available and provided novel estimates for phenotypes without prior twin studies or those assessed at different ages. Effects of site, self-identified race/ethnicity, age and sex were statistically controlled. Results from genetic modeling of all 53,172 continuous variables, including 38,672 functional MRI variables, will be accessible via the user-friendly open-access web interface we have established, and will be updated as new data are released from the ABCD Study. This paper provides an overview of the initial results from the twin study embedded within the ABCD Study, an introduction to the primary research domains in the ABCD study and twin methodology, and an evaluation of the initial findings with a focus on data quality and suitability for future behavior genetic studies using the ABCD dataset. The broad introductory material is provided in recognition of the multidisciplinary appeal of the ABCD Study. While this paper focuses on univariate analyses, we emphasize the opportunities for multivariate, developmental and causal analyses, as well as those evaluating heterogeneity by key moderators such as sex, demographic factors and genetic background.

Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis.

Despite the substantial heritability of antisocial behavior (ASB), specific genetic variants robustly associated with the trait have not been identified. The present study by the Broad Antisocial Behavior Consortium (BroadABC) meta-analyzed data from 28 discovery samples (N = 85,359) and five independent replication samples (N = 8058) with genotypic data and broad measures of ASB. We identified the first significant genetic associations with broad ASB, involving common intronic variants in the forkhead box protein P2 (FOXP2) gene (lead SNP rs12536335, p = 6.32 × 10-10). Furthermore, we observed intronic variation in Foxp2 and one of its targets (Cntnap2) distinguishing a mouse model of pathological aggression (BALB/cJ strain) from controls (BALB/cByJ strain). Polygenic risk score (PRS) analyses in independent samples revealed that the genetic risk for ASB was associated with several antisocial outcomes across the lifespan, including diagnosis of conduct disorder, official criminal convictions, and trajectories of antisocial development. We found substantial genetic correlations of ASB with mental health (depression rg = 0.63, insomnia rg = 0.47), physical health (overweight rg = 0.19, waist-to-hip ratio rg = 0.32), smoking (rg = 0.54), cognitive ability (intelligence rg = -0.40), educational attainment (years of schooling rg = -0.46) and reproductive traits (age at first birth rg = -0.58, father's age at death rg = -0.54). Our findings provide a starting point toward identifying critical biosocial risk mechanisms for the development of ASB.

Pubertal timing and adolescent outcomes: investigating explanations for associations with a genetically informed design.

BACKGROUND: Psychopathology and risky behaviors increase during adolescence, and understanding which adolescents are most at risk informs prevention and intervention efforts. Pubertal timing relative to same-sex, same-age peers is a known correlate of adolescent outcomes among both boys and girls. However, it remains unclear whether this relation is better explained by a plausible causal process or unobserved familial liability. METHODS: We extended previous research by examining associations between pubertal timing in early adolescence (age 14) and outcomes in later adolescence (age 17) in a community sample of 2,510 twins (49% boys, 51% girls). RESULTS: Earlier pubertal timing was associated with more substance use, risk behavior, internalizing and externalizing problems, and peer problems in later adolescence; these effects were small, consistent with previous literature. Follow-up co-twin control analyses indicated that within-twin-pair differences in pubertal timing were not associated with within-twin-pair differences in most adolescent outcomes after accounting for shared familial liability, suggesting that earlier pubertal timing and adolescent outcomes both reflect familial risk factors. Biometric models indicated that associations between earlier pubertal timing and negative adolescent outcomes were largely attributable to shared genetic liability. CONCLUSIONS: Although earlier pubertal timing was associated with negative adolescent outcomes, our results suggests that these associations did not appear to be caused by earlier pubertal timing but were likely caused by shared genetic influences.

The Concept of Resistance to Substance Use and a Research Approach: The Resist! Project.

Illicit substance use is dangerous in both acute and chronic forms, frequently resulting in lethal poisoning, addiction, and other negative consequences. Similar to research in other psychiatric conditions, whose ultimate goal is to enable effective prevention and treatment, studies in substance use are focused on factors elevating the risk for the disorder. The rapid growth of the substance use problem despite the effort invested in fighting it, however, suggests the need in changing the research approach. Instead of attempting to identify risk factors, whose neutralization is often infeasible if not impossible, it may be more promising to systematically reverse the perspective to the factors enhancing the aspect of liability to disorder that shares the same dimension but is opposite to risk, that is, resistance to substance use. Resistance factors, which enable the majority of the population to remain unaffected despite the ubiquity of psychoactive substances, may be more amenable to translation. While the resistance aspect of liability is symmetric to risk, the resistance approach requires substantial changes in sampling (high-resistance rather than high-risk) and using quantitative indices of liability. This article provides an overview and a practical approach to research in resistance to substance use/addiction, currently implemented in a NIH-funded project. The project benefits from unique opportunities afforded by the data originating from two longitudinal twin studies, the Virginia Twin Study of Adolescent and Behavioral Development and the Minnesota Twin Family Study. The methodology described is also applicable to other psychiatric disorders.

Personality and peer groups in adolescence: Reciprocal associations and shared genetic and environmental influences.

OBJECTIVE: Peer groups represent a critical developmental context in adolescence, and there are many well-documented associations between personality and peer behavior at this age. However, the precise nature and direction of these associations are difficult to determine as youth both select into, and are influenced by, their peers. METHOD: We thus examined the phenotypic, genetic, and environmental links between antisocial and prosocial peer characteristics and several personality traits from middle childhood to late adolescence (ages 11, 14, and 17 years) in a longitudinal twin sample (N = 3762) using teacher ratings of personality and self-reports of peer characteristics. RESULTS: Less adaptive trait profiles (i.e., high negative emotionality, low conscientiousness, and low agreeableness) were associated with more antisocial and fewer prosocial peer characteristics across time. Associations between personality traits related to emotionality (negative emotionality and extraversion) and peer behavior were largely attributable to shared genetic influences, while associations between personality traits related to behavioral control (conscientiousness and agreeableness) and peer behavior were due to overlapping genetic and shared environmental influences. CONCLUSIONS: Overall, results suggest a set of environmental presses that push youth toward both behavioral undercontrol and antisocial peer affiliations, making the identification of such influences and their relative importance a critical avenue of future work.

Addendum to "Evaluating substance use outcomes of recreational cannabis legalization using a unique co-twin control design".

An earlier version of this article was published in error. Our prior publication was missing reference to a prior study on this topic. Our prior research has not found an association between recreational cannabis legalization (RCL) and negative psychosocial and psychiatric outcomes. We reported significant associations between RCL with greater cannabis frequency and fewer alcohol use disorder symptoms. The current study expands on our previous research by using a cross-sectional design and different measures of problems from cannabis and alcohol use and including additional substance use variables. The current study found similar results to our previous research.

Evaluating substance use outcomes of recreational cannabis legalization using a unique co-twin control design.

Background: As more states pass recreational cannabis legalization (RCL), we must understand how RCL affects substance use.Objectives: The current study aims to examine the effect of RCL on lifetime and past-year use of cannabis, alcohol, tobacco, and other drugs, frequency of cannabis, alcohol, and tobacco use, co-use of cannabis with alcohol and tobacco, and consequences from cannabis and alcohol use.Methods: We used a unique, co-twin control design of twin pairs who were discordant for living in a state with RCL between 2018 and 2021. The sample consisted of 3,830 adult twins (41% male), including 232 twin pairs discordant for RCL. Problems from alcohol and cannabis use were assessed via the Brief Marijuana Consequences Questionnaire and the Brief Young Adult Alcohol Consequences Questionnaire.Results: Results indicated that the twin living in an RCL state was more likely to endorse past-year cannabis use (OR = 1.56, p = .009), greater number of cannabis use days in the past 6 months (ß = 0.47, p = .019), but not more negative consequences from cannabis use (ß = 0.21, p = .456) compared to their co-twin in a non-RCL state. There were no differences within-twin pairs in frequency of alcohol use (ß=-0.05, p = .601), but the RCL twin reported fewer negative consequences from alcohol use (ß=-0.29, p = .016) compared to their co-twin in a non-RCL state. We did not observe any other differences within-twin pairs on other outcomes.Conclusion: These results suggest that living in an RCL state is associated with greater cannabis frequency but not more negative consequences from cannabis use than living in a non-RCL state.

The association between saving disposition and financial distress: A genetically informed approach.

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.

The role of parental genotype in predicting offspring years of education: evidence for genetic nurture.

Similarities between parent and offspring are widespread in psychology; however, shared genetic variants often confound causal inference for offspring outcomes. A polygenic score (PGS) derived from genome-wide association studies (GWAS) can be used to test for the presence of parental influence that controls for genetic variants shared across generations. We use a PGS for educational attainment (EA3; N ≈ 750 thousand) to predict offspring years of education in a sample of 2517 twins and both parents. We find that within families, the dizygotic twin with the higher PGS is more likely to attain higher education (unstandardized ß = 0.32; p < 0.001). Additionally, however, we find an effect of parental genotype on offspring outcome that is independent of the offspring's own genotype; this raises the variance explained in offspring years of education from 9.3 to 11.1% (∆R2 = 0.018, p < 0.001). Controlling for parental IQ or socioeconomic status substantially attenuated or eliminated this effect of parental genotype. These findings suggest a role of environmental factors affected by heritable characteristics of the parents in fostering offspring years of education.

Longitudinal effects and environmental moderation of ALDH2 and ADH1B gene variants on substance use from age 14 to 40.

Alcohol use and dependence are strongly affected by variation in aldehyde dehydrogenase (ALDH2) and, to a lesser extent, alcohol dehydrogenase (ADH1B) genes. We use this genetic variation with an adoption design to test the causal role of alcohol use on other drug use, as well as the moderating role of adoptive parent, sibling, and peer alcohol use. Longitudinal models were run on 412 genotyped adopted individuals of East Asian ancestry with multiple assessments between ages 14 and 40. We found robust associations between alcohol frequency, quantity, and maximum drinks and ALDH2, but not ADH1B, status. The magnitude of the ALDH2 protective effect increased with age, particularly for maximum drinks, though estimates were smaller than previously reported in ancestrally similar individuals in East/North-East Asian countries. These results suggest that sociocultural factors in Minnesota may reduce the protective effects of ALDH2. We found that peer alcohol use, but not parent or sibling use, predicted adopted offspring's use, and that these environmental influences did not vary by ALDH2 status. Finally, we did not find strong evidence of associations between ALDH2 status and tobacco, marijuana, or illegal drug use, contrary to expectation if alcohol serves as a gateway to use of other drugs.

Exploring the possibility of parents' broad internalizing phenotype acting through passive gene-environment correlations on daughters' disordered eating.

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.

A Century of Behavioral Genetics at the University of Minnesota.

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.

The clashing nature of rebelliousness: Nontraditional attitudes and counter-normative behaviors show divergent associations with intelligence.

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.

Parent Contributions to the Development of Political Attitudes in Adoptive and Biological Families.

Where do our political attitudes originate? Although early research attributed the formation of such beliefs to parent and peer socialization, genetically sensitive designs later clarified the substantial role of genes in the development of sociopolitical attitudes. However, it has remained unclear whether parental influence on offspring attitudes persists beyond adolescence. In a unique sample of 394 adoptive and biological families with offspring more than 30 years old, biometric modeling revealed significant evidence for genetic and nongenetic transmission from both parents for the majority of seven political-attitude phenotypes. We found the largest genetic effects for religiousness and social liberalism, whereas the largest influence of parental environment was seen for political orientation and egalitarianism. Together, these findings indicate that genes, environment, and the gene-environment correlation all contribute significantly to sociopolitical attitudes held in adulthood, and the etiology and development of those attitudes may be more important than ever in today's rapidly changing sociopolitical landscape.

Parietal P3 and midfrontal theta prospectively predict the development of adolescent alcohol use.

BACKGROUND: Subclinical adolescent alcohol use is highly prevalent and may have deleterious effects on important psychosocial and brain outcomes. Prior research has focused on identifying endophenotypes of pathological drinking, and the predictors of normative drinking remain understudied. This study investigated the incremental predictive value of two potential psychophysiological endophenotypes, P3 amplitude (an index of decision making) and midfrontal theta power (a correlate of attentional control), for prospectively predicting the expression and initiation of alcohol use emerging in adolescence. METHODS: A large (N = 594) epidemiological sample was prospectively assessed at ages 11/14/17. Alcohol/substance use was assessed at all ages via a computerized self-report inventory. EEG was recorded at age-14 during a visual oddball task to elicit P3 and theta. RESULTS: Reduced target-related P3 and theta at age-14 prospectively predicted drinking at age-17 independent of one another. Among alcohol-naive individuals at age-14, attenuated P3 and theta increased the odds of new-onset alcohol behaviors 3 years later. Importantly, the endophenotypes provided significant incremental predictive power of future non-clinical alcohol use beyond relevant risk factors (prior alcohol use; tobacco/illicit drug initiation; parental alcohol use disorder). CONCLUSIONS: The current report is the first of our knowledge to demonstrate that deviations in parietal P3 and midfrontal theta prospectively predict the emergence of normative/non-pathological drinking. P3 and theta provide modest yet significant explanatory variance beyond prominent self-report and familial risk measures. Findings offer strong evidence supporting the predictive utility of P3 and theta as candidate endophenotypes for adolescent drinking.