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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 Skłodowska-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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, couse 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Time–frequency representations of electroencephalographic signals lend themselves to a granular analysis of cognitive and psychological processes. Characterizing developmental trajectories of time–frequency measures can thus inform us about the development of the processes involved as well as correlated traits and behaviors. We decomposed electroencephalographic (EEG) activity in a large sample of individuals (N = 1692; 917 females), assessed at approximately 3‐year intervals from the age of 11 to their mid‐20s. Participants completed an oddball task that elicits a robust P3 response. Principal component analysis served to identify the primary dimensions of time–frequency energy. Component loadings were virtually identical across assessment waves. A common and stable set of time–frequency dynamics thus characterized EEG activity throughout this age range. Trajectories of changes in component scores suggest that aspects of brain development reflected in these components comprise two distinct phases, with marked decreases in component amplitude throughout much of adolescence followed by smaller yet significant rates of decreases into early adulthood. Although the structure of time–frequency activity was stable throughout adolescence and early adulthood, we observed subtle change in component loadings as well. Our findings suggest that striking developmental change in event‐related potentials emerges through a gradual change in the magnitude and timing of a stable set of dimensions of time–frequency activity, illustrating the usefulness of time–frequency representations of EEG signals and longitudinal designs for understanding brain development. In addition, we provide proof of concept that trajectories of time‐frequency activity can serve as potential endophenotypes for childhood externalizing psychopathology and alcohol use in adolescence and early adulthood. Our findings suggest that a striking change in event‐related potentials in adolescence and early adulthood emerges through a gradual change in the magnitude and timing of a stable set of dimensions of time–frequency activity. These results illustrate the usefulness of time–frequency representations of EEG signals as well as longitudinal designs for understanding brain development. In addition, we provide proof of concept that developmental trajectories can serve as candidate endophenotypes for disinhibited behavior. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: To better characterize brain-based mechanisms of polygenic liability for psychopathology and psychological traits, we extended our previous report (Liu et al. Psychophysiological endophenotypes to characterize mechanisms of known schizophrenia genetic loci. Psychological Medicine, 2017), focused solely on schizophrenia, to test the association between multivariate psychophysiological candidate endophenotypes (including novel measures of θ / δ oscillatory activity) and a range of polygenic scores (PGSs), namely alcohol/cannabis/nicotine use, an updated schizophrenia PGS (containing 52 more genome-wide significant loci than the PGS used in our previous report) and educational attainment. Method: A large community-based twin/family sample (N = 4893) was genome-wide genotyped and imputed. PGSs were constructed for alcohol use, regular smoking initiation, lifetime cannabis use, schizophrenia, and educational attainment. Eleven endophenotypes were assessed: visual oddball task event-related electroencephalogram (EEG) measures (target-related parietal P3 amplitude, frontal θ , and parietal δ energy/inter-trial phase clustering), band-limited resting-state EEG power, antisaccade error rate. Principal component analysis exploited covariation among endophenotypes to extract a smaller number of meaningful dimensions/components for statistical analysis. Results: Endophenotypes were heritable. PGSs showed expected intercorrelations (e.g. schizophrenia PGS correlated positively with alcohol/nicotine/cannabis PGSs). Schizophrenia PGS was negatively associated with an event-related P3/ δ component [ β = −0.032, nonparametric bootstrap 95% confidence interval (CI) −0.059 to −0.003]. A prefrontal control component (event-related θ /antisaccade errors) was negatively associated with alcohol (β = −0.034, 95% CI −0.063 to −0.006) and regular smoking PGSs (β = −0.032, 95% CI −0.061 to −0.005) and positively associated with educational attainment PGS (β = 0.031, 95% CI 0.003–0.058). Conclusions: Evidence suggests that multivariate endophenotypes of decision-making (P3/ δ) and cognitive/attentional control (θ /antisaccade error) relate to alcohol/nicotine, schizophrenia, and educational attainment PGSs and represent promising targets for future research. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Aims: Molecular genetic studies of alcohol and nicotine use have identified many genome‐wide association study (GWAS) loci. We measured associations between drinking and smoking polygenic scores (PGS) and trajectories of alcohol and nicotine use outcomes from late childhood to early adulthood, substance‐specific versus broader‐liability PGS effects, and if PGS performance varied for consumption versus problematic substance use. Design, setting, participants and measurements: We fitted latent growth curve models with structured residuals to scores on measures of alcohol and nicotine use and problems from ages 14 to 34 years. We then estimated associations between the intercept (initial status) and slope (rate of change) parameters and PGSs for drinks per week (DPW), problematic alcohol use (PAU), cigarettes per day (CPD) and ever being a regular smoker (SMK), controlling for sex and genetic principal components. All data were analyzed in the United States. PGSs were calculated for participants of the Minnesota Twin Family Study (n = 3225) using results from the largest GWAS of alcohol and nicotine consumption and problematic use to date. Findings Each PGS was associated with trajectories of use for their respective substances [i.e. DPW (βmean = 0.08; βrange = 0.02–0.12) and PAU (βmean = 0.12; βrange = −0.02 to 0.31) for alcohol; CPD (βmean = 0.08; βrange = 0.04–0.14) and SMK (βmean = 0.18; βrange = 0.05–0.36) for nicotine]. The PAU and SMK PGSs also exhibited cross‐substance associations (i.e. PAU for nicotine‐specific intercepts and SMK for alcohol intercepts and slope). All identified SMK PGS effects remained as significant predictors of nicotine and alcohol trajectories (βmean = 0.15; βrange = 0.02–0.33), even after adjusting for the respective effects of all other PGSs. Conclusions: Substance use‐related polygenic scores (PGSs) vary in the strength and generality versus specificity of their associations with substance use and problems over time. The regular smoking PGS appears to be a robust predictor of substance use trajectories and seems to measure both nicotine‐specific and non‐specific genetic liability for substance use, and potentially externalizing problems in general. [ABSTRACT FROM AUTHOR]

Background/aims: Research linking orbitofrontal cortex (OFC) structure and substance use disorders (SUDs) is largely correlational and often implies a causal effect of addiction/substance exposure on the brain, but familial risk factors (e.g. genetic liability) may confound these associations. We tested whether associations between alcohol, cannabis and tobacco use disorders and OFC thickness reflected the potential causal effects of familial risk or SUDs‐related consequences (e.g. substance exposure). Design A co‐twin control/discordant twin design separated familial risk confounding from SUD‐related consequences. Setting/participants: A population‐based sample of 436 24‐year‐old twins (62% monozygotic) from the Minnesota Twin Family Study, USA. Measurements Alcohol, cannabis and tobacco use disorders were assessed using the Composite International Diagnostic Interview—Substance Abuse Module. Cortical thickness of the medial and lateral OFC (mOFC and lOFC, respectively) was assessed using magnetic resonance imaging (MRI). Findings Lower mOFC (P‐values ≤ 0.006) but not lOFC (P‐values ≥ 0.190) thickness was observed in diagnosed individuals (n = 185) relative to non‐SUD controls (n = 251). Co‐twin control analyses offered evidence that mOFC associations were consistent with familial risk across SUDs (between‐pair effect: P‐values ≤ 0.047) and the independent consequences of having an alcohol or cannabis use disorder (within‐pair effect: P‐values ≤ 0.024). That is, within alcohol/cannabis discordant twin pairs, affected twins had significantly lower mOFC thickness compared with their unaffected co‐twins. Conclusions: A confounder‐adjusted analysis of the Minnesota Twin Family Study appeared to indicate that, beyond a substance use disorders general familial risk effect, the experience of an alcohol or cannabis use disorder in emerging adulthood reduces the thickness of the medial orbitofrontal cortex, a region associated with value‐guided decision‐making. [ABSTRACT FROM AUTHOR]

Educational success is associated with greater quality of life and depends, in part, on heritable cognitive and non-cognitive traits. We used polygenic scores (PGS) for smoking and educational attainment to examine different genetic influences on facets of academic adjustment in adolescence and educational attainment in adulthood. PGSs were calculated for participants of the Minnesota Twin Family Study (N = 3225) and included as predictors of grades, academic motivation, and discipline problems at ages 11, 14, and 17 years-old, cigarettes per day from ages 14 to 24 years old, and educational attainment in adulthood (mean age 29.4 years). Smoking and educational attainment PGSs had significant incremental associations with each academic variable and cigarettes per day. About half of the adjusted effects of the smoking and education PGSs on educational attainment in adulthood were mediated by the academic variables in adolescence. Cigarettes per day from ages 14 to 24 years old did not account for the effect of the smoking PGS on educational attainment, suggesting the smoking PGS indexes genetic influences related to general behavioral disinhibition. In sum, distinct genetic influences measured by the smoking and educational attainment PGSs contribute to academic adjustment in adolescence and educational attainment in adulthood. [ABSTRACT FROM AUTHOR]

Background and aims: Social context is an important factor in determining the developmental trajectory of alcohol use. We examined the co‐development between alcohol use problems and antisocial peer affiliation. We also estimated the genetic and environmental influences on alcohol use problems, antisocial peer affiliation and their co‐development over time. Design Longitudinal study using bivariate latent basis models with structured residuals (LBM‐SR). A biometric model was then fitted to estimate the genetic and environmental influences on the growth factors and their covariances. Setting: The United States mid‐west region. Participants: Members of the Minnesota Twin Family Study (MTFS), an ongoing, longitudinal study of 3762 (52% female) twins (1881 pairs). Measurements: Alcohol use problems were assessed using a composite measure of average number of drinks per occasion in the past 12 months, maximum number of drinks in 24 hours and DSM‐III‐R symptoms of alcohol abuse and dependence. Antisocial peer affiliation was measured by self‐report of the proportion of one's friends who exhibited types of antisocial behaviors. Findings The LBM‐SR model revealed that there was a large correlation between the growth factors for alcohol use problems and antisocial peer affiliation [r = 0.78, 95% confidence interval (CI) = 0.76, 0.80] and cross‐lagged effects consistent with both selection and socialization effects. Additionally, antisocial peer affiliation in adolescence was associated with greater increases in alcohol use problems over time (r = 0.57, 95% CI = 0.54, 0.60). Genetic influences largely accounted for the association between antisocial peer affiliation in pre‐adolescence and growth in alcohol use problems, while shared environmental influences accounted for the correlation between antisocial peer affiliation and alcohol use problems growth factors. Conclusions: Antisocial peer affiliation in adolescence appears to be a salient, genetically influenced risk factor for early alcohol use and increase in alcohol use from adolescence to young adulthood. [ABSTRACT FROM AUTHOR]

Background and aims: Existing evidence for a link between alcohol use and memory impairments in adolescents and young adults is largely correlational. We aimed to determine whether associations between drinking and episodic memory were consistent with a causal effect of drinking or accounted for by familial factors confounding such associations. Because cannabis use is associated with a similar pattern of performance on episodic memory measures, we assessed whether any associations might be attributable to concurrent cannabis use. Design, setting and participants: Observational study of individuals aged approximately 20–29 years, comprising two independent population‐based cohorts of twins. A co‐twin–control design permitted an estimate of alcohol exposure effects free of shared genetic and environmental confounding influences. Significant associations were followed‐up with twin‐difference analyses. Propensity scores derived from measures collected at age 11 were used to adjust for unshared confounders. Participants in both cohorts were assessed from the age of 11 (n = 1251) under the auspices of the Minnesota Center for Twin and Family Research. Measurements Regression analyses with cumulative alcohol use as the predictor of interest. Multiple measures of attention, learning and memory from a widely used episodic memory task constituted dependent variables. Findings Drinking was associated with poorer attention (P ≤ 0.003) and learning (P ≤ 0.008). Results were similar across the two cohorts. The within‐pair effect in twin‐difference analyses was significant only for measures of learning (P‐values ≤ 0.004). Results were not due to measured unshared confounders or cannabis use. Drinking in adolescence (to age 20) and early adulthood (between 20 and 29) exerted independent effects on learning. Conclusions: There appears to be a robust and specific association between drinking and learning that can be reproduced across cohorts, is not easily accounted for by confounding factors or concurrent cannabis use and is consistent with a causal influence of drinking. [ABSTRACT FROM AUTHOR]

Objective: College attainment is one of the few phenotypes to have substantial variance accounted for by environmental factors shared by reared-together relatives. The shared environment is implicated by the consistently strong parent-to-offspring transmission of college attainment. The mechanisms underlying this relationship remain unclear. We use genetically informative methods with a longitudinal, adoption sample to identify possible environmental mechanisms underlying parent-offspring college transmission.Method: Data were drawn from the Sibling Interaction and Behavior Study (SIBS), which includes 409 adoptive and 208 nonadoptive families, consisting of two offspring followed from adolescence into young adulthood and their rearing parents. Four domains of environmental mechanisms were examined: (a) skill enhancement; (b) academic support; (c) material advantage; and (d) supportive family environment.Results: Both shared environmental and genetic factors contributed to the parent-offspring transmission of college attainment. However, highly educated parents did not appear to be increasing their adopted offspring's attainment through skill development. The environmental factors that were associated with increased odds of offspring college attainment were mother's academic expectations and family income.Conclusions: While complete mediation of the parent-offspring transmission of college attainment was not identified, the results shed light on some of the mechanisms associated with the common environment variance in the college attainment phenotype. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Peer groups influence the emergence of sexual behaviors in adolescence, but many details regarding the mechanisms underlying these effects have yet to be described. We examined the phenotypic, genetic, and environmental links between both antisocial and prosocial peer characteristics, and several sexual behaviors from middle childhood to late adolescence (ages 11, 14, and 17 years) using a longitudinal twin sample (N = 3762). Antisocial peers predicted greater engagement in both normative (e.g., dating) and non-normative (e.g., early sexual intercourse) sexual behaviors, while prosocial peers were associated with a lower likelihood of engaging in non-normative sexual behaviors. Reciprocal effects were also observed such that early sexual experiences were associated with a more antisocial and less prosocial peer groups later in adolescence. Behavioral genetic models indicated that most of the overlap between peer group characteristics and sexual behavior was due to shared environmental influences. That is, some features of the adolescent environment exert a press toward (or against) antisocial peers and sexual behaviors. Together, the results extend the existing literature by highlighting the ways through which peer affiliations are related to sexual development in adolescence. [ABSTRACT FROM AUTHOR]

Prior research has shown that person-level characteristics (e.g., temperament, personality) correlate and interact with social-contextual factors (e.g., parent–child relationship quality, antisocial peer affiliation) to predict adolescent substance use, but less research has examined similar processes for adult substance use problems. We addressed this gap by testing for personality × romantic partner context interplay in relation to symptoms of alcohol use disorder (AUD) at ages 24 and 29. Participants were twins in the longitudinal Minnesota Twin Family Study (N = 2,769; 52% female). Results support the corresponsive principle of personality in that we found that key personality traits in late adolescence (low constraint, negative emotionality) predicted subsequent "selection" into key social contexts in early adulthood (poorer quality romantic relationships and greater romantic partner alcohol use), which subsequently reinforced those traits and associated outcomes (including correlated AUD symptoms) through late young adulthood. There were few meaningful gender differences in these associations. There was also no support for the personality × romantic partner context interaction as a significant predictor of AUD symptoms at ages 24 or 29. Taken together with prior studies, these results suggest that such interactions may be less relevant to the development of young adult AUD compared to adolescent substance use problems. [ABSTRACT FROM AUTHOR]

Background: Parental characteristics and practices predict borderline personality disorder (BPD) symptoms in children. However, it is difficult to disentangle whether these effects are genetically or environmentally mediated. The present study examines the contributions of genetic and environmental influences by comparing the effects of familial risk factors (i.e. parental psychopathology and borderline traits, maladaptive parenting, marital discord) on child BPD traits in genetically related (biological) and non-related (adoptive) families. Methods: Data are from 409 adoptive and 208 biological families who participated in the Siblings Interaction and Behavior Study (SIBS) and 580 twin families the Minnesota Twin Family Study (MTFS). Parent characteristics and practices included parental psychopathology (measured via structured clinical interviews), parental BPD traits, parenting behaviors, and marital discord. A series of multi-level regression models were estimated to examine the relationship of familial risk factors to child BPD traits and to test whether children's adoptive status moderated the association. Results: Symptom counts of parents' conduct disorder, adult antisocial behavior, nicotine, alcohol, and illicit drug dependence, and paternal BPD traits substantially predicted child BPD traits only in biological offspring, implying genetic transmission. Maternal BPD traits and both maternal and paternal conflict, lack of regard, and lack of involvement predicted offspring BPD traits regardless of the adoptive status, implying environmental transmission. Conclusions: Parental externalizing psychopathology and father's BPD traits contribute genetic risk for offspring BPD traits, but mothers' BPD traits and parents' poor parenting constitute environmental risks for the development of these offspring traits. [ABSTRACT FROM AUTHOR]

Sexual development entails many experiences and is a major feature of adolescence. Most relevant behavioral genetic studies, however, focus primarily on sexual behaviors associated with health risks. We took a more normative, developmental perspective by examining genetic and environmental influences on five sexual behaviors ranging from dating to pregnancy in middle (Mage = 14.90 years) and late adolescence (Mage = 17.85 years) in a sample of twins (N = 3,762). Overall, behaviors that are more common and socially sanctioned (e.g., dating) were more heritable than behaviors that are less common and socially acceptable (e.g., sexual intercourse). That the etiology of different sexual behaviors is tied to their normativeness highlights the importance of considering the broader developmental context when studying sexual development. [ABSTRACT FROM AUTHOR]

Externalizing psychopathology in early adolescence is a highly heritable risk factor for drug use, yet how it relates to marijuana use development is not well-characterized. We evaluate this issue in independent twin samples from Colorado (N = 2608) and Minnesota (N = 3630), assessed from adolescence to early adulthood. We used a biometric latent growth model of marijuana use frequency with data from up to five waves of assessment from ages 14 to 30, to examine change in marijuana use and its relationship with a factor model of adolescent externalizing psychopathology. The factor structure of adolescent externalizing psychopathology was similar across samples, as was the association between that common factor and early marijuana use (Minnesota r = 0.67 [0.60, 0.75]; Colorado r = 0.69 [0.59, 0.78]), and increase in use (Minnesota r = 0.18 [0.10, 0.26]; Colorado r = 0.20 [0.07, 0.34]). Early use was moderately heritable in both samples (Minnesota h2 = 0.57 [0.37, 0.79]; Colorado h2 = 0.42 [0.14, 0.73]). Increase in use was highly heritable in Minnesota (h2 = 0.82 [0.72, 0.88]), less so in Colorado (h2 = 0.22 [0.01, 0.66]), and shared environmental effects were larger in Colorado (c2 = 0.55 [0.14, 0.83]) than Minnesota (c2 = 0 [0, 0.06]). We found moderate genetic correlations between externalizing psychopathology and early use in both samples. Finally, additional analyses in the Minnesota sample indicated that marijuana use decreased during the late 20s. This decline is strongly heritable (h2 = 0.73 [0.49, 0.91]) and moderately negatively correlated with adolescent externalizing psychopathology (r = − 0.41 [− 0.54, − 0.28]). Adolescent externalizing psychopathology is genetically correlated with change in late adolescent marijuana use (late teens, early 20s), as well as maintenance of use in early adulthood (late 20 s) even after controlling for the effects of early use. [ABSTRACT FROM AUTHOR]

Research suggests major mental disorders co-occur at higher than chance levels. In adult samples, a two factor structure emerges when modeling the higher order structure of psychopathology. Specifically, disorders tend to co-aggregate into two dimensions: Internalizing (depression and anxiety) and Externalizing (acting out, impulsive, and addictive) disorders. Despite this large body of evidence, few studies have integrated problem gambling into this overall model. We used confirmatory factor analysis to model how the symptom count of gambling fits into the structure of psychopathology in a large, community based young adult twin sample of men and women (age 24; N = 1329). Twins were assessed via in-person, structured diagnostic interviews on disorders including: Major Depression, Phobias, Post-Traumatic Stress Disorder and Anxiety Disorders (internalizing) and Substance Use Disorders, Gambling Problems (self-report), and Antisocial Behaviors (externalizing). The data were fit to a two-factor structure, with gambling symptoms loading most highly on externalizing, rather than internalizing. The problem gambling loadings did not differ by sex. Implications of these findings suggest that during emerging adulthood gambling problems are best classified and conceptualized in the realm of externalizing disorders for both males and females. Results also suggest prevention and intervention efforts be aimed at young adults who exhibit commonly co-occurring psychopathology. [ABSTRACT FROM AUTHOR]

The current study examined how discrimination relates to adjustment outcomes in a sample of internationally, transracially adopted Korean Americans from the Minnesota Sibling Interaction and Behavior Study (N = 456 adoptees; Mage at T1 = 14.9, Mage at T2 = 18.3, Mage at T3 = 22.3). The moderating roles of ethnic socialization and preparation for bias by parents (i.e., ethnic-racial socialization) were also examined. Results indicated that discrimination predicted higher levels of depressive and externalizing symptoms in youth who reported less preparation for bias. In those experiencing more preparation for bias, associations were not significantly different from zero. Ethnic socialization did not moderate these associations. Such findings provide important information for adoptive parents regarding how to prepare their children to cope with discrimination. [ABSTRACT FROM AUTHOR]

The Minnesota Center for Twin and Family Research (MCTFR) comprises multiple longitudinal, community-representative investigations of twin and adoptive families that focus on psychological adjustment, personality, cognitive ability and brain function, with a special emphasis on substance use and related psychopathology. The MCTFR includes the Minnesota Twin Registry (MTR), a cohort of twins who have completed assessments in middle and older adulthood; the Minnesota Twin Family Study (MTFS) of twins assessed from childhood and adolescence into middle adulthood; the Enrichment Study (ES) of twins oversampled for high risk for substance-use disorders assessed from childhood into young adulthood; the Adolescent Brain (AdBrain) study, a neuroimaging study of adolescent twins; and the Siblings Interaction and Behavior Study (SIBS), a study of adoptive and nonadoptive families assessed from adolescence into young adulthood. Here we provide a brief overview of key features of these established studies and describe new MCTFR investigations that follow up and expand upon existing studies or recruit and assess new samples, including the MTR Study of Relationships, Personality, and Health (MTR-RPH); the Colorado-Minnesota (COMN) Marijuana Study; the Adolescent Brain Cognitive Development (ABCD) study; the Colorado Online Twins (CoTwins) study and the Children of Twins (CoT) study. [ABSTRACT FROM AUTHOR]

Previous research has shown that problematic parent–child, peer, and romantic partner relationships are associated with an increased likelihood for major depressive disorder (MDD). Less research has evaluated the developmental unfolding of how these interpersonal relationship features are both an antecedent versus a consequence of MDD symptoms from adolescence through young adulthood. These gaps were evaluated using a large community sample (N = 1,127; 54% female, 96% white) via a developmental cascade model. Results showed support for significant antecedent effects, as greater parent–child relationship problems at ages 11 and 17 predicted rank-order increases in MDD symptoms at ages 14 and 20. Supporting a developmental cascade of problematic social relationships, greater parent–child relationship problems at ages 11 and 14 also predicted greater subsequent rank-order increases in antisocial peer affiliation at ages 14 and 17. Greater affiliation to antisocial peers at age 20 predicted greater rank-order increases in romantic relationship problems at age 24, which in turn predicted greater MDD symptoms at age 29. Cross-effects were generally small (βs ≤.16), illustrating other factors may be relevant to the development or consequences of MDD. Nonetheless, findings support the importance of efforts to strengthen social support networks to offset risk as well as potentially treat depression. [ABSTRACT FROM AUTHOR]

Though theory suggests that individual differences in neuroticism (a tendency to experience negative emotions) would be associated with altered functioning of the amygdala (which has been linked with emotionality and emotion dysregulation in childhood, adolescence, and adulthood), results of functional neuroimaging studies have been contradictory and inconclusive. We aimed to clarify the relationship between neuroticism and three hypothesized neural markers derived from functional magnetic resonance imaging during negative emotion face processing: amygdala activation, amygdala habituation, and amygdala-prefrontal connectivity, each of which plays an important role in the experience and regulation of emotions. We used general linear models to examine the relationship between trait neuroticism and the hypothesized neural markers in a large sample of over 500 young adults. Although neuroticism was not significantly associated with magnitude of amygdala activation or amygdala habituation, it was associated with amygdala–ventromedial prefrontal cortex connectivity, which has been implicated in emotion regulation. Results suggest that trait neuroticism may represent a failure in top-down control and regulation of emotional reactions, rather than overactive emotion generation processes, per se. These findings suggest that neuroticism, which has been associated with increased rates of transdiagnostic psychopathology, may represent a failure in the inhibitory neurocircuitry associated with emotion regulation. [ABSTRACT FROM AUTHOR]

The fact that genes and environment contribute differentially to variation in human behaviors, traits and attitudes is central to the field of behavior genetics. Perceptions about these differential contributions may affect ideas about human agency. We surveyed two independent samples (N = 301 and N = 740) to assess beliefs about free will, determinism, political orientation, and the relative contribution of genes and environment to 21 human traits. We find that lay estimates of genetic influence on these traits cluster into four distinct groups, which differentially predict beliefs about human agency, political orientation, and religiosity. Despite apparent ideological associations with these beliefs, the correspondence between mean lay estimates and published heritability estimates for the surveyed traits is large (r = .77). Belief in genetic determinism emerges as a modest predictor of accuracy in these lay estimates. Additionally, educated mothers with multiple children emerge as particularly accurate in their estimates of the genetic contribution to these traits. [ABSTRACT FROM AUTHOR]

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 crosssectional 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. [ABSTRACT FROM AUTHOR]

Few studies have investigated potential gender differences in the genetic and environmental influences on the prospective associations between parent-child conflict and later depression, a notable gap given substantial gender differences in rates of depression and suggestive evidence of differences in the etiology of depression among females and males. To fill this gap, we evaluated whether the prospective relationship between parent-child conflict and major depressive disorder symptoms varied as a function of parent-child gender composition. A combined twin and adoption sample was used (53% female; 85% European ancestry), containing 1,627 adolescent sibling pairs (789 monozygotic twin pairs, 594 dizygotic/full-biological pairs, 244 genetically unrelated pairs) with assessments at two time points in adolescence (approximate ages 15 and 18). Prospective associations between parent-child conflict and subsequent adolescent depression were explained predominately through common genetic influences for mother-daughter and mother-son pairs but less so for father-daughter and father-son pairs. Results support the notion that processes of gene-environment correlation involved in the prospective associations between parent-child conflict, and later adolescent depression appear to be less relevant to father-child relationships in comparison to mother-child relationships. Notably, results did not show that parent-child conflict was more relevant to the etiology of major depressive disorder (MDD) for girls than boys; gender differences in depression do not appear to be due to differences in the associations between parent-child conflict and child depression. [ABSTRACT FROM AUTHOR]

Background: We examined whether increased risk for adolescent tobacco and marijuana problems associated with childhood ADHD is explained by key intermediary influences during adolescence and differs by gender. Methods: Longitudinal structural equation models examined mediating effects on problems with both substances (or each substance separately) through age‐14 peer impairment, internalizing, and adolescent ADHD symptoms in two twin samples, prospectively assessed since age 11 (N = 2,164). Whether these mediators contributed beyond mediating effects of early‐adolescent substance use was also considered. Twin difference analyses further illuminated which mediators might be potentially causal. Results: Direct effects of childhood ADHD on age‐17 tobacco and marijuana problems (i.e., independent of included mediators) as well as effects of adolescent ADHD symptoms were significant only for females. By contrast, mediation by peer impairment, evident particularly for marijuana, was relatively stronger for males than females. Depression and anxiety were not prospectively associated with age‐17 substance problems when earlier substance problems were considered. Consistent with causal influence of early substance use on later problems, monozygotic twins with more severe tobacco or marijuana problems at age 14 than their co‐twins were also more likely to have substance problems later in adolescence. Conclusions: Mediation through peer impairment, continued presence of ADHD symptoms, and early substance use may alter development so that childhood ADHD indirectly contributes to problems with tobacco and marijuana. Targeting gender‐sensitive interventions prior to mid‐adolescence, before these patterns become established, is essential. [ABSTRACT FROM AUTHOR]

Background: In the United States, cannabis accessibility has continued to rise as the perception of its harmfulness has decreased. Only about 30% of regular cannabis users develop cannabis use disorder (CUD), but it is unclear if individuals who use cannabis regularly without ever developing CUD experience notable psychosocial impairment across the lifespan. Therefore, psychosocial functioning was compared across regular cannabis users with or without CUD and a non-user control group during adolescence (age 17; early risk) and young adulthood (ages 18–25; peak CUD prevalence). Method: Weekly cannabis users with CUD (n = 311), weekly users without CUD (n = 111), and non-users (n = 996) were identified in the Minnesota Twin Family Study. Groups were compared on alcohol and illicit drug use, psychiatric problems, personality, and social functioning at age 17 and from ages 18 to 25. Self-reported cannabis use and problem use were independently verified using co-twin informant report. Results: In both adolescence and young adulthood, non-CUD users reported significantly higher levels of substance use problems and externalizing behaviors than non-users, but lower levels than CUD users. High agreement between self- and co-twin informant reports confirmed the validity of self-reported cannabis use problems. Conclusions: Even in the absence of CUD, regular cannabis use was associated with psychosocial impairment in adolescence and young adulthood. However, regular users with CUD endorsed especially high psychiatric comorbidity and psychosocial impairment. The need for early prevention and intervention – regardless of CUD status – was highlighted by the presence of these patterns in adolescence. [ABSTRACT FROM AUTHOR]

Background: Although there is extensive evidence that problematic alcohol use is associated with smaller hippocampal volume, the typical cross-sectional study design cannot determine whether hippocampal deviations reflect pre-existing liability toward problematic alcohol use or instead reflect an alcohol exposure-related effect. We used the co-twin control study design, which capitalizes upon differences within a twin pair in levels of drinking, to differentiate pre-existing liability from an effect of alcohol exposure. Methods: The sample included 100 female twins, prospectively assessed from ages 11 to 24. Problematic alcohol use was assessed dimensionally and included indicators of quantity, frequency, and density of alcohol use and intoxication. Hippocampal volume was assessed using magnetic resonance imaging. Results: Problematic alcohol use (proximal and cumulative) was associated with significantly smaller left and right hippocampal volume. Follow-up co-twin control analyses that partitioned individual-level alcohol effects into pre-existing, familial liability and non-shared alcohol exposure-related effects indicated that this association reflected alcohol exposure. Greater alcohol using twins had smaller hippocampal volume relative to lesser alcohol using co-twins, beyond effects of their shared genetic and environmental liability toward problematic alcohol use. Results held accounting for recent alcohol use, other substance use, externalizing and internalizing psychopathology, personality traits, trauma exposure, and menstrual phase. Conclusions: The association between problematic alcohol use and smaller hippocampal volume likely reflects an alcohol exposure-related effect. Differentiating pre-existing brain deviations that confer risk for problematic alcohol use from those that reflect effects of alcohol on the brain will inform etiological models of addiction and further prevention and intervention efforts. [ABSTRACT FROM AUTHOR]

Meta-analysis of genetic association studies increases sample size and the power for mapping complex traits. Existing methods are mostly developed for datasets without missing values, i.e. the summary association statistics are measured for all variants in contributing studies. In practice, genotype imputation is not always effective. This may be the case when targeted genotyping/sequencing assays are used or when the un-typed genetic variant is rare. Therefore, contributed summary statistics often contain missing values. Existing methods for imputing missing summary association statistics and using imputed values in meta-analysis, approximate conditional analysis, or simple strategies such as complete case analysis all have theoretical limitations. Applying these approaches can bias genetic effect estimates and lead to seriously inflated type-I or type-II errors in conditional analysis, which is a critical tool for identifying independently associated variants. To address this challenge and complement imputation methods, we developed a method to combine summary statistics across participating studies and consistently estimate joint effects, even when the contributed summary statistics contain large amounts of missing values. Based on this estimator, we proposed a score statistic called PCBS (partial correlation based score statistic) for conditional analysis of single-variant and gene-level associations. Through extensive analysis of simulated and real data, we showed that the new method produces well-calibrated type-I errors and is substantially more powerful than existing approaches. We applied the proposed approach to one of the largest meta-analyses to date for the cigarettes-per-day phenotype. Using the new method, we identified multiple novel independently associated variants at known loci for tobacco use, which were otherwise missed by alternative methods. Together, the phenotypic variance explained by these variants was 1.1%, improving that of previously reported associations by 71%. These findings illustrate the extent of locus allelic heterogeneity and can help pinpoint causal variants. [ABSTRACT FROM AUTHOR]

Objective: Personality traits related to negative emotionality and low constraint are strong correlates of alcohol use disorder (AUD), but few studies have evaluated the prospective interplay between these traits and AUD symptoms from adolescence to young adulthood.Method: The Minnesota Twin Family Study (N = 2,769) was used to examine the developmental interplay between AUD symptoms and three personality measures of constraint, negative emotionality, and aggressive undercontrol from ages 17 to 29.Results: Results from random-intercept, cross-lagged panel models showed that low constraint and aggressive undercontrol predicted subsequent rank-order increases in AUD symptoms from ages 17 to 24. AUD symptoms did not predict rank-order change in these traits from ages 17 to 24. There was support for both cross-effects from ages 24 to 29. Biometric analysis of the twin data showed genetic influences accounted for most of the phenotypic correlations over time.Conclusion: Results are consistent with the notion that personality traits related to low constraint and aggressive undercontrol are important vulnerability/predisposition factors for the development of early adult AUD. In later young adulthood, there is more evidence for the simultaneous codevelopment of personality and AUD. Implications are addressed with attention to personality-based risk assessments and targeted AUD prevention approaches. [ABSTRACT FROM AUTHOR]

Previous research has reported correlations between the military service records of parents and their children. Those studies, however, have not determined whether a parent’s military service causally influences an offspring’s participation in the armed forces. To investigate the possibility of a causal relationship, we examined whether lottery numbers issued to draft-eligible men during the U.S. Vietnam-era Selective Service Lotteries influenced the military participation of those men’s children. Our study found higher rates of military participation among children born to fathers whose randomly assigned numbers were called for induction. Furthermore, we perform statistical analyses indicating that the influence of lottery numbers on the subsequent generation’s military participation operated through the military service of draft-eligible men as opposed to mechanisms unrelated to service such as “draft dodging.” These findings provide evidence of a causal link between the military service of parents and their children. [ABSTRACT FROM AUTHOR]

Although borderline personality disorder (BPD) traits decline from adolescence to adulthood, comorbid psychopathology such as symptoms of major depressive disorder (MDD), alcohol use disorder (AUD), and drug use disorders (DUDs) likely disrupt this normative decline. Using a longitudinal sample of female twins (N=1,763), we examined if levels of BPD traits were correlated with changes in MDD, AUD, and DUD symptoms from ages 14 to 24. A parallel process biometric latent growth model examined the contributions of genetic and environmental factors to the relationships between developmental components of these phenotypes. Higher BPD trait levels predicted a greater rate of increase in AUD and DUD symptoms, and higher AUD and DUD symptoms predicted a slower rate of decline of BPD traits from ages 14 to 24. Common genetic influences accounted for the associations between BPD traits and each disorder, as well as the interrelationships of AUD and DUD symptoms. Both genetic and nonshared environmental influences accounted for the correlated levels between BPD traits and MDD symptoms, but solely environmental influences accounted for the correlated changes between the two over time. Results indicate that higher levels of BPD traits may contribute to an earlier onset and faster escalation of AUD and DUD symptoms, and substance use problems slow the normative decline in BPD traits. Overall, our data suggests that primarily genetic influences contribute to the comorbidity between BPD features and substance use disorder symptoms.We discuss our data in the context of two major theories of developmental psychopathology and comorbidity. [ABSTRACT FROM AUTHOR]

Research has long demonstrated that siblings are similar in their alcohol use, however much of this work relies on cross-sectional samples or samples of adolescents alone and/or exclusive focus on older siblings’ impact on younger siblings. Using a three time-point design from early adolescence to early adulthood (M ages = 14.9, 18.3, and 22.4 years, respectively; 55% female; 54% European ancestry, 38% Asian ancestry), we evaluated the prospective older and younger sibling influences on alcohol use across time (N = 613 sibling pairs; 35% sisters, 26% brothers, 39% mixed-gender; average age difference = 2.34 years; 34% full-biological siblings, 46% genetically-unrelated adopted siblings, 20% pairs where one child was the biological offspring of parents and the other was adopted). The results from both the traditional and random-intercept cross-lagged panel analyses showed that older siblings’ alcohol use predicted younger siblings’ alcohol use across each developmental transition and across a variety of sibling contexts (e.g., gender composition, age difference, genetic relatedness). On the other hand, younger siblings’ alcohol use only predicted older siblings’ alcohol use when siblings were close in age (1.5 years or less) and under conditions of high sibling companionship. These results add to a body of literature illustrating how both older and younger siblings are important socializing agents of adolescent and early adult alcohol use. Assessing or co-treating siblings for alcohol problems may be an important add-on to existing adolescent and early adult alcohol prevention and intervention programs. [ABSTRACT FROM AUTHOR]

Objective: This study examined the effects of childhood attention deficit hyperactivity disorder (ADHD) symptoms, both inattention and hyperactivity-impulsivity, on the development of smoking in male and female adolescents.Method: Twin difference methods were used to control for shared genetic and environmental confounders in three population-based, same-sex twin samples (N=3,762; 64% monozygotic). One cohort oversampled female adolescents with ADHD beginning in childhood. Regressions of childhood inattentive and hyperactive-impulsive symptoms were conducted to predict smoking outcomes by age 17. ADHD effects were divided into those shared between twins in the pair and those nonshared, or different within pairs.Results: Adolescents who had more severe ADHD symptoms as children were more likely to initiate smoking and to start smoking younger. The association of ADHD symptoms with daily smoking, number of cigarettes per day, and nicotine dependence was greater in females than in males. Monozygotic female twins with greater attentional problems than their co-twins had greater nicotine involvement, consistent with possible causal influence. These effects remained when co-occurring externalizing behaviors and stimulant medication were considered. Hyperactivity-impulsivity, while also more strongly related to smoking for female adolescents, appeared primarily noncausal.Conclusions: Smoking initiation and escalation are affected differentially by ADHD subtype and gender. The association of inattention with smoking in female adolescents may be causal, whereas hyperactivity-impulsivity appears to act indirectly, through shared propensities for both ADHD and smoking. [ABSTRACT FROM AUTHOR]

Research indicates that alcohol misuse is associated with behavioral disinhibition, but the neurophysiological mechanisms governing this relationship remain largely unknown. Recent work suggests that successful inhibition and cognitive control involve electrophysiological theta-band dynamics, including medial frontal cortex (MFC) power enhancement and functional connectivity between the MFC and dorsal prefrontal cortex (dPFC) regions, which may be disrupted by alcohol misuse. In addition, research suggests that, compared to men, women are at heightened risk of experiencing the negative physical and neurocognitive correlates of drinking. The present study tested the hypothesis that alcohol misuse has a deleterious effect on theta-band response inhibition EEG dynamics in a sample of 300 24-year-old same-sex twins. A cotwin control (CTC) design was used to disentangle premorbid risk for alcohol use from the causal effects of alcohol exposure. Drinking was negatively associated with theta-band MFC power and MFC-dPFC connectivity during response inhibition, and this effect was stronger among women. The CTC analysis suggested that, for women, reduced nogo-related theta-band MFC power and MFC-dPFC connectivity were both consistent with the potential deleterious causal effects of alcohol exposure. These findings suggest that diminished theta-band MFC power and MFC-dPFC connectivity may be neurophysiological mechanisms underlying alcohol-related disinhibition. Although preliminary, these results suggest that normative levels of alcohol use during emerging adulthood have potential sex-specific causal effects on response inhibition EEG dynamics, and thus have potentially significant public health implications. [ABSTRACT FROM AUTHOR]

While the P3 component during target detection and novelty processing has been widely studied, less is known about its underlying network dynamics. A recent cognitive model suggests that frontal-parietal and frontal-temporal interregional connectivity are related to attention/action selection and target-related memory updating during the P3, respectively, but empirical work testing this model is lacking. Other work suggests the importance of theta- and delta-band connectivity between the medial frontal cortex and distributed cortical regions during attention, stimulus detection, and response selection processes, and similar dynamics may underlie P3- related network connectivity. The present study evaluated the functional connectivity elicited during a visual task, which combined oddball target and novelty stimuli, in a sample of 231 same-sex twins. It was hypothesized that both target and novel conditions would involve theta frontoparietal connectivity and medial frontal theta power, but that target stimuli would elicit the strongest frontotemporal connectivity. EEG time-frequency analysis revealed greater theta-band frontoparietal connectivity and medial frontal power during both target and novel conditions compared to standards, which may index conflict/uncertainty resolution processes. Theta-band frontotemporal connectivity was maximal during the target condition, potentially reflecting context updating or stimulus-response activation. Delta-band frontocentral-parietal connectivity was also strongest following targets, which may be sensitive to response-related demands. These results suggest the existence of functional networks related to P3 that are differentially engaged by target oddballs and novel distractors. Compared to simple P3 amplitude, network measures may provide a more nuanced view of the neural dynamics during target detection/novelty processing in normative and pathological populations. [ABSTRACT FROM AUTHOR]

Previous research has established that parental marital discord is associated with higher levels of offspring externalizing behaviors, but it is unclear how parental relationship functioning is associated with the genetic and environmental variance on a factor of externalizing problems. Thus, the current study assessed how parental marital discord moderates genetic and environmental variance on offspring externalizing problems at two different ages: childhood and late adolescence. That is, the magnitude of genetic and environmental influences on offspring externalizing at ages 11 and 17 was examined as a function of parental marital discord. Consistent with a diathesis–stress model of psychopathology, it was hypothesized that with increasing marital discord, genetic influences on externalizing would be more pronounced. Rather, results indicated that for the 11-year-old sample, nonshared environmental influences were greater when parental marital discord was low, and comparatively, shared environmental influences contributed more to the variance in externalizing problems when parental marital discord was high. No moderation was found for the 17-year-old cohort. In contrast to studies that do not find an effect of the shared environment, these results provide evidence that the common rearing environment has an impact on externalizing problems in preadolescent children. [ABSTRACT FROM AUTHOR]