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Objective: Examine the nature of the relationship between adolescent polysubstance use and high school noncompletion., Method: Among a sample of 9,579 adult Australian twins (58.63% female, M age = 30.59), we examined the association between the number of substances used in adolescence and high school noncompletion within a discordant twin design and bivariate twin analysis., Results: In individual-level models controlling for parental education, conduct disorder symptoms, childhood major depression, sex, zygosity, and cohort, each additional substance used in adolescence was associated with a 30% increase in the odds of high school noncompletion ( OR = 1.30 [1.18, 1.42]). Discordant twin models found that the potentially causal effect of adolescent use on high school noncompletion was nonsignificant ( OR = 1.19 [0.96, 1.47]). Follow-up bivariate twin models suggested genetic (35.4%, 95% CI [24.5%, 48.7%]) and shared environmental influences (27.8%, 95% CI [12.7%, 35.1%]) each contributed to the covariation in adolescent polysubstance use and early school dropout., Conclusions: The association between polysubstance use and early school dropout was largely accounted for by genetic and shared environmental factors, with nonsignificant evidence for a potentially causal association. Future research should examine whether underlying shared risk factors reflect a general propensity for addiction, a broader externalizing liability, or a combination of the two. More evidence using finer measurement of substance use is needed to rule out a causal association between adolescent polysubstance use and high school noncompletion. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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., (© 2022. The Author(s).)

Previous research has shown that self-reports of the amount of social support are heritable. Using the Kessler perceived social support (KPSS) measure, we explored sex differences in the genetic and environmental contributions to individual differences. We did this separately for subscales that captured the perceived support from different members of the network (spouse, twin, children, parents, relatives, friends and confidant). Our sample comprised 7059 male, female and opposite-sex twin pairs aged 18-95 years from the Australian Twin Registry. We found tentative support for different genetic mechanisms in males and females for support from friends and the average KPSS score of all subscales, but otherwise, there are no sex differences. For each subscale alone, the additive genetic (A) and unique environment (E) effects were significant. By contrast, the covariation among the subscales was explained - in roughly equal parts - by A, E and the common environment, with effects of different support constellations plausibly accounting for the latter. A single genetic and common environment factor accounted for between half and three-quarters of the variance across the subscales in both males and females, suggesting little heterogeneity in the genetic and environmental etiology of the different support sources.

Objective: The present study updates prior research, incorporating state-level administrative data to examine associations between self-reported history of alcohol dependence and birth record-derived reproductive onset, the latter assessed through peak childbearing years., Method: Participants included 542 African ancestry (AA) and 2,928 European or other ancestry (EA) female twins ascertained through Missouri birth records and recruited as part of a birth cohort study of like-sex female pairs born between 1975 and 1985. Analyses were limited to twins for whom residence in Missouri when of reproductive age could be documented, including twins who left Missouri but later returned. Cox proportional hazards regression models were estimated predicting age at first childbirth from history of alcohol dependence, separately for AA and EA twins, without and with adjustment for sociodemographic characteristics, comorbid psychopathology and other substance involvement, overweight/obesity status, and family-of-origin and childhood risk factors., Results: Among EA twins, alcohol dependence predicted both early and delayed childbearing; in adjusted models, alcohol dependence was associated with overall delayed childbearing. Associations between alcohol dependence and reproductive onset were nonsignificant among AA twins., Conclusions: Findings for EA twins are consistent with the broader literature indicating increased risk of teen motherhood associated with early-onset and problem drinking, but suggest that this may be explained by other correlated risk factors. The more robust finding, confirming relatively recent research, is of delayed childbearing associated with alcohol dependence.

Drinking alcohol is a normal behavior in many societies, and prior studies have demonstrated it has both genetic and environmental sources of variation. Using two very large samples of twins and their first-degree relatives (Australia ≈ 20,000 individuals from 8,019 families; Virginia ≈ 23,000 from 6,042 families), we examine whether there are differences: (1) in the genetic and environmental factors that influence four interrelated drinking behaviors (quantity, frequency, age of initiation, and number of drinks in the last week), (2) between the twin-only design and the extended twin design, and (3) the Australian and Virginia samples. We find that while drinking behaviors are interrelated, there are substantial differences in the genetic and environmental architectures across phenotypes. Specifically, drinking quantity, frequency, and number of drinks in the past week have large broad genetic variance components, and smaller but significant environmental variance components, while age of onset is driven exclusively by environmental factors. Further, the twin-only design and the extended twin design come to similar conclusions regarding broad-sense heritability and environmental transmission, but the extended twin models provide a more nuanced perspective. Finally, we find a high level of similarity between the Australian and Virginian samples, especially for the genetic factors. The observed differences, when present, tend to be at the environmental level. Implications for the extended twin model and future directions are discussed.

Background: Childhood maltreatment is a known risk factor for cannabis initiation and problem use, but the extent to which this association is attributable to shared familial influences is unknown. We estimate the magnitude of associations between childhood maltreatment, timing of cannabis initiation, and cannabis-related problems, in European-American (EA) and African-American (AA) women, and parse the relative influence of additive genetic (A), shared environmental (C), and individual-specific environmental (E) factors on these constructs and their covariation., Methods: Data were from diagnostic telephone interviews conducted with 3786 participants (14.6% AA) in a population-based study of female twins. Logistic regression analyses and twin modeling were used to test for associations, and estimate the relative contributions of genetic and environmental influences to childhood maltreatment and cannabis outcomes and their covariation., Results: Maltreatment was significantly associated with increased likelihood of cannabis initiation before age 15 among EAs (OR=6.33) and AAs (OR=3.93), but with increased likelihood of later initiation among EAs only (OR=1.68). Maltreatment was associated with cannabis problems among both groups (EA OR=2.32; AA OR=2.03). Among EA women, the covariation between maltreatment and cannabis outcomes was primarily attributable to familial environment (rC=0.67-0.70); among AAs, only individual-specific environment contributed (rE=0.37-0.40)., Conclusion: Childhood maltreatment is a major contributor to early initiation of cannabis as well as progression to cannabis problems in both AA and EA women. Distinctions by race/ethnicity are not in the relative contribution of genetic factors, but rather in the type of environmental influences that contribute to stages of cannabis involvement., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Early and frequent cannabis use are associated with an increased likelihood of major depressive disorder (MDD) as well as suicidal thoughts and behaviours. We identify associations between aspects of cannabis use, MDD, and suicidal thoughts and behaviours and examine whether such associations persist after accounting for those predisposing factors, including genetic liability and early family environment, that are shared by identical twins who are discordant for cannabis exposure. Any residual association in such identical pairs might be indicative of individual-specific pathways that might be of a causal nature., Methods: We did a logistic regression analysis of cannabis use from retrospective data on same-sex male and female twin pairs drawn from 3 studies that had recruited twins from the Australian Twin Registry, 1992-93 (sample 1), 1996-2000 (sample 2), and 2005-09 (sample 3). We studied associations between early use and frequent use of cannabis and MDD, suicidal ideation (ever and persistent), and suicide plan and attempt in the full sample as well as in pairs of monozygotic and dizygotic twins that were discordant for each measure of cannabis involvement at a single timepoint. Significant monozygotic associations were further adjusted for covariates, such as early alcohol or nicotine use, early dysphoric or anhedonic mood, conduct disorder, and childhood sexual abuse. Interactions between each cannabis measure and sex, sample or study effects, and birth year category were also examined as covariates., Findings: In 13 986 twins (6181 monozygotic and 7805 dizygotic), cannabis use ranged from 1345 (30·4%) of 4432 people in sample 1 to 2275 (69·0%) of 3299 in sample 3. Mean age of first cannabis use ranged from 17·9 years (SD 3·3) in sample 3 to 21·1 years (5·2) in sample 1, and frequent use (≥100 times) was reported by 214 (15·9%) of 1345 users in sample 1 and 499 (21·9%) of 2275 in sample 3. The prevalence of suicidal ideation ranged from 1102 (24·9%) of 4432 people in sample 1 to 1644 (26·3%) of 6255 people in sample 2 and 865 (26·2%) of 3299 people in sample 3. Prevalence of MDD ranged from 901 (20·3%) people in sample 1 to 1773 (28·3%) in sample 2. The monozygotic twin who used cannabis frequently was more likely to report MDD (odds ratio 1·98, 95% CI 1·11-3·53) and suicidal ideation (2·47, 1·19-5·10) compared with their identical twin who had used cannabis less frequently, even after adjustment for covariates. For early cannabis use, the monozygotic point estimate was not significant but could be equated to the significant dizygotic estimate, suggesting a possible association with suicidal ideation., Interpretation: The increased likelihood of MDD and suicidal ideation in frequent cannabis users cannot be solely attributed to common predisposing factors., Funding: National Institute on Drug Abuse, National Institutes of Health, Australian National Health and Medical Research Council., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background and Objectives: We examined the associations of religious attendance during childhood (C-RA) and adulthood (A-RA) with alcohol involvement (ever drinking, timing of first alcohol use, and alcohol use disorder [AUD]) in White and Black female twins. As genetic and environmental factors influence religious attendance and alcohol involvement, we examined the extent to which they contribute to their association., Methods: Data on 3,234 White and 553 Black female twins (18-29 years) from the Missouri Adolescent Female twin Study. Significant correlations between C-RA or A-RA and alcohol involvement were parsed into their additive genetic, shared environmental, and individual-specific environmental sources., Results: C-RA was associated with ever drinking and timing of first alcohol use in Whites. A-RA was associated with ever drinking and AUD in both Whites and Blacks. Shared environmental influences did not contribute to alcohol or religiosity phenotypes in Blacks. In Whites, the association between C-RA and alcohol was due to shared environmental influences, whereas the association between A-RA and alcohol was attributable to additive genetic, shared environmental, and individual-specific environmental sources. Individual-specific environment and genetics contributed to associations between A-RA and ever drinking and AUD, respectively, in Blacks., Conclusions: Factors other than C-RA contribute to lower rates of alcohol involvement in Blacks. Shared environment does not contribute to links between A-RA and alcohol involvement in Blacks., Scientific Significance: The protective impact of childhood religiosity on alcohol use and misuse is important in Whites and is due to familial factors shared by religiosity and alcohol involvement. (Am J Addict 2017;26:437-445)., (© 2016 American Academy of Addiction Psychiatry.)

The ability to inhibit prepotent but context- or goal-inappropriate responses is essential for adaptive self-regulation of behavior. Deficits in response inhibition, a key component of impulsivity, have been implicated as a core dysfunction in a range of neuropsychiatric disorders such as ADHD and addictions. Identification of genetically transmitted variation in the neural underpinnings of response inhibition can help to elucidate etiological pathways to these disorders and establish the links between genes, brain, and behavior. However, little is known about genetic influences on the neural mechanisms of response inhibition during adolescence, a developmental period characterized by weak self-regulation of behavior. Here we investigated heritability of ERPs elicited in a Go/No-Go task in a large sample of adolescent twins assessed longitudinally at ages 12, 14, and 16. Genetic analyses showed significant heritability of inhibition-related frontal N2 and P3 components at all three ages, with 50 to 60% of inter-individual variability being attributable to genetic factors. These genetic influences included both common genetic factors active at different ages and novel genetic influences emerging during development. Finally, individual differences in the rate of developmental changes from age 12 to age 16 were significantly influenced by genetic factors. In conclusion, the present study provides the first evidence for genetic influences on neural correlates of response inhibition during adolescence and suggests that ERPs elicited in the Go/No-Go task can serve as intermediate neurophysiological phenotypes (endophenotypes) for the study of disinhibition and impulse control disorders., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Cannabis use, particularly at an early age, has been linked to suicidal thoughts and behavior, but minimal work has examined the association between cannabis use and lifetime nonsuicidal self-injury (NSSI). The current study aims to characterize the overlap between lifetime and early cannabis use and NSSI and to examine genetic and environmental mechanisms of this association., Method: Adult male and female twins from the Australian Twin Registry (N = 9,583) were used to examine the odds of NSSI associated with lifetime cannabis use and early cannabis use (i.e., <17 years of age). These associations were also examined within monozygotic (MZ) twins discordant for cannabis use and MZ twins discordant for early cannabis use. Analyses were replicated in an independent sample of female twins (n = 3,787) accounting for the age at onset of cannabis use and NSSI., Results: Lifetime cannabis use (odds ratio [OR] = 2.84, 95% CI [2.23, 3.61]) and early cannabis use were associated with increased odds of NSSI (OR = 2.15, 95% CI [1.75, 2.65]), and this association remained when accounting for covariates. The association was only significant, however, in MZ twin pairs discordant for early cannabis use (OR = 3.20, 95% CI [1.17, 8.73]). Replication analyses accounting for the temporal ordering of cannabis use and NSSI yielded similar findings of nominal significance., Conclusions: Results suggest that NSSI is associated with cannabis involvement via differing mechanisms. For lifetime cannabis use, the lack of association in discordant pairs suggests the role of shared genes and family environment. However, in addition to such shared familial influences, person-specific and putatively causal factors contribute to the relationship between early cannabis use and NSSI. Therefore, delaying the onset of cannabis use may reduce exposure to influences that exacerbate vulnerabilities to NSSI.

Background: Use of cigarettes and cannabis frequently co-occurs. We examine the role of genetic and environmental influences on variation in and covariation between tobacco cigarette and cannabis use across European-American (EA) and African-American (AA) women., Methods: Data on lifetime cannabis and cigarette use were drawn from interviews of 956 AA and 3557 EA young adult female twins and non-twin same sex female full siblings. Twin modeling was used to decompose variance in and covariance between cigarette and cannabis use into additive genetic, shared, special twin and non-shared environmental sources., Results: Cigarette use was more common in EAs (75.3%, 95% C.I. 73.8-76.7%) than AAs (64.2%, 95% C.I. 61.2-67.2%) while cannabis use was marginally more commonly reported by AAs (55.5%, 95% C.I. 52.5-58.8%) than EAs (52.4%, 95% C.I. 50.7-54.0%). Additive genetic factors were responsible for 43-66% of the variance in cigarette and cannabis use. Broad shared environmental factors (shared+special twin) played a more significant role in EA (23-29%) than AA (2-15%) women. In AA women, the influence of non-shared environment was more pronounced (42-45% vs. 11-19% in EA women). There was strong evidence for the same familial influences underlying use of both substances (rA=0.82-0.89; rC+T=0.70-0.75). Non-shared environmental factors were also correlated but less so (rE=0.48-0.66). No racial/ethnic differences were apparent in these sources of covariation., Conclusion: Heritability of cigarette and cannabis use is comparable across racial/ethnic groups. Differences in the contribution of shared and non-shared environmental influences indicate that different factors may shape substance use in EA and AA women., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

To investigate familial influences on the full range of variability in attention and activity across adolescence, we collected maternal ratings of 339 twin pairs at ages 12, 14, and 16, and estimated the transmitted and new familial influences on attention and activity as measured by the Strengths and Weaknesses of Attention-Deficit/Hyperactivity Disorder Symptoms and Normal Behavior Scale. Familial influences were substantial for both traits across adolescence: genetic influences accounted for 54%-73% (attention) and 31%-73% (activity) of the total variance, and shared environmental influences accounted for 0%-22% of the attention variance and 13%-57% of the activity variance. The longitudinal stability of individual differences in attention and activity was largely accounted for by familial influences transmitted from previous ages. Innovations over adolescence were also partially attributable to familial influences. Studying the full range of variability in attention and activity may facilitate our understanding of attention-deficit/hyperactivity disorder's etiology and intervention.

Studies of maternal smoking during pregnancy (MSDP) suggest increased risk for cognitive impairment and psychiatric outcomes. However, it is uncertain whether these associations are the direct result of MSDP or related to confounding familial variables associated with MSDP. The current study employed propensity score analysis to examine the effects of MSDP on offspring EXT using data from a large sample of 979 unrelated mothers. Logistic regression models were used to determine the propensity that the offspring of these mothers were likely to be exposed to MSDP [i.e., smoked during only the first trimester (MSDP-EARLY[E]) or smoked throughout their pregnancy (MSDP-THROUGHOUT[T])] given known familial confounders. Analyses focused on the effect of MSDP-E/T on the EXT behavior in offspring of these mothers (N = 1616) were conducted across the distribution of liability for MSDP-E/T and at different levels of risk for MSDP-E/T. MSDP-E/T was associated with offspring EXT problems, but the effects were partly confounded by the familial liability for MSDP. Further, the observed effects were not consistent across all levels of the MSDP risk distribution. These findings suggest a direct association between MSDP and offspring EXT behaviors, and that varied associations observed across studies may be the result of differences in the level of familial confounders that also have an effect on offspring EXT.

Background: Despite substantial evidence that alcohol use disorder (AUD) and bulimic behaviors (i.e., binge eating and compensatory behaviors) co-occur, insufficient information exists regarding a possible shared etiology. Moreover, although numerous twin studies of European ancestry individuals have reported moderate heritability estimates for AUD and bulimic behaviors, with little evidence for shared environmental factors, research on genetic and environmental risk in African American (AA) individuals is lacking., Methods: We investigated specific and overlapping genetic and environmental influences on AUD and bulimic behaviors in 3232 European American (EA; 55.38% monozygotic) and 549 AA (42.81% monozygotic) young adult female twins from the Missouri Adolescent Female Twin Study (age range=18-29 years). A structured clinical interview assessed lifetime DSM-5 AUD (minus craving) and bulimic behaviors. Biometrical twin modeling was conducted to generate age-adjusted estimates of genetic and environmental influences on AUD, bulimic behaviors, and their comorbidity., Results: Estimates of genetic and environmental contributions on AUD and bulimic behaviors could be equated across EA and AA women. Additive genetic effects accounted for 59% (95% CI: 50%, 66%) and 43% (33%, 52%) of the variance in AUD and bulimic behaviors, respectively, with the remainder due to non-shared environmental effects. Shared genetic factors (rg=.33 (.18, .49)) were solely responsible for the correlation between phenotypes; the non-shared environmental correlation was not significant (re=.10 (-.05, .25))., Conclusions: Findings indicate similar magnitudes of genetic and environmental effects on AUD and bulimic behaviors for EA and AA women and implicate common genetic mechanisms underlying liability to these problem behaviors., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Purpose: We examined timing of first voluntary sexual intercourse as a joint function of parental separation during childhood and parental history of alcoholism., Methods: Data were drawn from a birth cohort of female like-sex twins (n = 569 African ancestry [AA]; n = 3,415 European or other ancestry [EA]). Cox proportional hazards regression was conducted predicting age at first sex from dummy variables coding for parental separation and parental alcoholism. Propensity score analysis was also employed to compare intact and separated families, stratified by predicted probability of separation., Results: Earlier sex was reported by EA twins from separated and alcoholic families, compared to EA twins from intact nonalcoholic families, with effects most pronounced through the age of 14 years. Among AA twins, effects of parental separation and parental alcoholism were largely nonsignificant. Results of propensity score analyses confirmed unique risks from parental separation in EA families, where consistent effects of parental separation were observed across predicted probability of separation. For AA families, there was poor matching on risk factors presumed to predate separation, which limited interpretability of survival-analytic findings., Conclusions: In European American families, parental separation during childhood is an important predictor of early-onset sex, beyond parental alcoholism and other correlated risk factors. To characterize risk for African Americans associated with parental separation, additional research is needed where matching on confounders can be achieved., (Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Aspects of disordered eating and personality traits, such as neuroticism, are correlated and individually heritable. We examined the phenotypic correlation between binge eating episodes and indices of personality (neuroticism, extraversion, openness to experience, agreeableness, conscientiousness, and control/impulsivity). For correlations ≥|0.20|, we estimated the extent to which genetic and environmental factors contributed to this correlation. Participants included 3,446 European American same-sex female twins from the Missouri Adolescent Female Twin Study (median age = 22 years). Binge eating episode was assessed via interview questions. Personality traits were assessed by self-report questionnaires. There was a significant moderate phenotypic correlation between binge eating episode and neuroticism (r = 0.33) as well as conscientiousness (r = -0.21), while other correlations were significant but smaller (r ranging from -0.14 to 0.14). Individual differences in binge eating episodes, neuroticism, and conscientiousness were attributed to additive genetic influences (38% [95% CI: 21-53%], 45% [95% CI: 38-52%], and 44% [95% CI: 0.33-0.55%] respectively), with the remaining variance attributed to individual-specific environmental influences. Covariance was attributable to genetic (neuroticism r g = 0.37; conscientiousness r g = -0.22) and individual-specific environmental (neuroticism r e = 0.28; conscientiousness r e = -0.19) influences. Personality traits may be an early indicator of genetic vulnerability to a variety of pathological behaviors, including binge eating episode. Furthermore, prior research documenting phenotypic correlations between eating disorder diagnoses and personality may have stemmed from etiological overlap between these personality traits and aspects of disordered eating, such as binge eating episode.

Background: Risks associated with parental separation have received limited attention in research on children of parents with substance use disorders. We examined early substance involvement as a function of parental separation during childhood and parental alcohol and cannabis dependence., Method: Data were drawn from 1318 adolescent offspring of monozygotic (MZ) or dizygotic (DZ) Australian twin parents. Cox proportional hazards regression analyses were conducted predicting age at first use of alcohol, first alcohol intoxication, first use and first regular use of cigarettes, and first use of cannabis, from parental separation and both parent and cotwin substance dependence. Parent and cotwin alcohol and cannabis dependence were initially modeled separately, with post hoc tests for equality of effects., Results: With few exceptions, risks associated with parental alcohol versus cannabis dependence could be equated, with results largely suggestive of genetic transmission of risk from parental substance (alcohol or cannabis) dependence broadly defined. Controlling for parental substance dependence, parental separation was a strong predictor for all substance use variables, especially through age 13., Conclusion: Together, findings underscore the importance of parental separation as a risk-factor for early substance involvement over and above both genetic and environmental influences specific to parental alcohol and cannabis dependence., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: Rates of alcohol dependence are elevated in women with eating disorders who engage in binge eating or compensatory behaviors compared with women with eating disorders who do not report binge eating or compensatory behaviors and with healthy controls. Alcohol dependence, binge eating, and compensatory behaviors are heritable; however, it is unclear whether a shared genetic liability contributes to the phenotypic association among these traits, and little information exists regarding this shared liability in men. We investigated genetic and environmental correlations among alcohol dependence, binge eating, and compensatory behaviors in male and female twins., Method: Participants included 5,993 same- and opposite-sex twins from the Australian Twin Registry who completed a modified version of the Semi-Structured Assessment for the Genetics of Alcoholism that assessed lifetime alcohol dependence and binge eating as defined in the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised. Compensatory behaviors were assessed via a general health questionnaire in women only. Biometrical twin models estimated genetic and environmental influences on alcohol dependence, binge eating, and compensatory behaviors., Results: In women, the multivariate twin model suggested that additive genetic and nonshared environmental effects influenced alcohol dependence, binge eating, and compensatory behaviors, with heritability estimates ranging from 38% to 53%. The best-fitting sex-limitation model was a common effects model that equated all genetic and nonshared environmental influences in men and women. The heritability estimates were 50% and 38% for alcohol dependence and binge eating, respectively. Overall, there were significant genetic correlations between alcohol dependence and binge eating, alcohol dependence and compensatory behaviors, and binge eating and compensatory behaviors., Conclusions: These findings indicate that common genetic factors may underlie the vulnerability to alcohol dependence and the liability to binge eating and compensatory behaviors.

Objective: Although the genetic contribution to the development of anorexia nervosa (AN) has long been recognized, there has been little progress relative to other psychiatric disorders in identifying specific susceptibility genes. Here, we have carried out a genome-wide association study on an unselected community sample of female twins surveyed for eating disorders., Method: We conducted genome-wide association analyses in 2,564 female twins for four different phenotypes derived from self-report data relating to lifetime presence of 15 types of disordered eating: AN spectrum, bulimia nervosa (BN) spectrum, purging via substances, and a binary measure of no disordered eating behaviors versus three or more. To complement the variant level results, we also conducted gene-based association tests using VEGAS software., Results: Although no variants reached genome-wide significance at the level of p < 10(-8), six regions were suggestive (p < 5 × 10(-7)). The current results implicate the following genes: CLEC5A, LOC136242, TSHZ1, and SYTL5 for the AN spectrum phenotype; NT5C1B for the BN spectrum phenotype; and ATP8A2 for the disordered eating behaviors phenotype., Discussion: As with other medical and psychiatric phenotypes, much larger samples and meta-analyses will ultimately be needed to identify genes and pathways contributing to predisposition to eating disorders., (© 2013 Wiley Periodicals, Inc.)

Background: Genetic risk for alcohol dependence has been shown to overlap with genetic factors contributing to variation in dimensions of personality. Although drinking motives have been posited as important mediators of the alcohol-personality relation, the extent to which the genetic covariance between alcohol use disorder (AUD) symptoms (i.e., abuse and dependence criteria) and personality is explained by genetic factors contributing to variation in drinking motives remains unclear., Methods: Using data from 2,904 young adult female twins, the phenotypic and genetic associations between personality dimensions (constraint [measured by the Multidimensional Personality Questionnaire; Tellegen A, 1982 unpublished data], conscientiousness, neuroticism, and agreeableness [measured by the NEO-PI; Costa and McCrae, 1985]), internal drinking motives (enhancement and coping motives [measured by the Drinking Motive Questionnaire; Cooper, 1994]), and AUD symptoms were tested., Results: Significant genetic associations were found between all personality measures and AUD symptoms. Coping motives showed significant genetic overlap with AUD symptoms and most personality measures, whereas enhancement motives were not significantly heritable. Adjusting for coping motives, genetic correlations between AUD symptoms and traits of neuroticism and agreeableness were no longer statistically significant., Conclusions: Findings suggest that genetic variation in drinking to cope might account for a considerable proportion of the genetic covariance between specific personality dimensions and AUD symptoms., (Copyright © 2011 by the Research Society on Alcoholism.)

Early-onset alcohol use is associated with increased vulnerability to subsequent alcohol abuse and dependence. However, not all early-onset alcohol users develop alcohol use disorders (AUDs). Using a sample of young women from the United States, we identify correlates that contribute to a greater likelihood of AUDs in early-onset alcohol users. Using interview and questionnaire data on participants of the Missouri Adolescent Female Twin Study (MOAFTS), we examine whether measures from domains including sociodemographic, pubertal development, religiosity, educational achievement, adverse life events, internalizing disorders, externalizing disorders, and family history and discipline were associated with development of AUDs in 1,158 women who had their first drink of alcohol prior to age 16. Early-onset drinkers were 3.6 times more likely to meet criteria for AUDs than later onset drinkers. While univariate analyses revealed that a host of correlates were associated with likelihood of AUDs in early-onset drinkers, multivariate analyses suggested that, even after accounting for a particularly early age of onset of drinking, those with a history of physical abuse, cotwin alcohol problems, conduct disorder, regular smoking, older peers, and peer substance use were considerably more likely to meet criteria for AUDs than early-onset drinkers without a lifetime history of these correlates. The progression from first drink to AUDs is complex, and while early age at first drink is a potent risk factor, other aspects of psychopathology, family history, conduct problems, and peer affiliations can exacerbate or alleviate the risk of AUDs in these young female drinkers., (© American Academy of Addiction Psychiatry.)

The human gut microbiota harbors three main groups of H(2)-consuming microbes: methanogens including the dominant archaeon, Methanobrevibacter smithii, a polyphyletic group of acetogens, and sulfate-reducing bacteria. Defining their roles in the gut is important for understanding how hydrogen metabolism affects the efficiency of fermentation of dietary components. We quantified methanogens in fecal samples from 40 healthy adult female monozygotic (MZ) and 28 dizygotic (DZ) twin pairs, analyzed bacterial 16S rRNA datasets generated from their fecal samples to identify taxa that co-occur with methanogens, sequenced the genomes of 20 M. smithii strains isolated from families of MZ and DZ twins, and performed RNA-Seq of a subset of strains to identify their responses to varied formate concentrations. The concordance rate for methanogen carriage was significantly higher for MZ versus DZ twin pairs. Co-occurrence analysis revealed 22 bacterial species-level taxa positively correlated with methanogens: all but two were members of the Clostridiales, with several being, or related to, known hydrogen-producing and -consuming bacteria. The M. smithii pan-genome contains 987 genes conserved in all strains, and 1,860 variably represented genes. Strains from MZ and DZ twin pairs had a similar degree of shared genes and SNPs, and were significantly more similar than strains isolated from mothers or members of other families. The 101 adhesin-like proteins (ALPs) in the pan-genome (45 ± 6 per strain) exhibit strain-specific differences in expression and responsiveness to formate. We hypothesize that M. smithii strains use their different repertoires of ALPs to create diversity in their metabolic niches, by allowing them to establish syntrophic relationships with bacterial partners with differing metabolic capabilities and patterns of co-occurrence.

Variation in personality traits is 30-60% attributed to genetic influences. Attempts to unravel these genetic influences at the molecular level have, so far, been inconclusive. We performed the first genome-wide association study of Cloninger's temperament scales in a sample of 5117 individuals, in order to identify common genetic variants underlying variation in personality. Participants' scores on Harm Avoidance, Novelty Seeking, Reward Dependence, and Persistence were tested for association with 1,252,387 genetic markers. We also performed gene-based association tests and biological pathway analyses. No genetic variants that significantly contribute to personality variation were identified, while our sample provides over 90% power to detect variants that explain only 1% of the trait variance. This indicates that individual common genetic variants of this size or greater do not contribute to personality trait variation, which has important implications regarding the genetic architecture of personality and the evolutionary mechanisms by which heritable variation is maintained., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background and Objectives: An excess of toxic trace elements or a deficiency of essential ones has been implicated in many common diseases or public health problems, but little is known about causes of variation between people living within similar environments. We estimated effects of personal and socioeconomic characteristics on concentrations of arsenic (As), cadmium (Cd), copper (Cu), mercury (Hg), lead (Pb), selenium (Se), and zinc (Zn) in erythrocytes and tested for genetic effects using data from twin pairs., Methods: We used blood samples from 2,926 adult twins living in Australia (1,925 women and 1,001 men; 30-92 years of age) and determined element concentrations in erythrocytes by inductively coupled plasma-mass spectrometry. We assessed associations between element concentrations and personal and socioeconomic characteristics, as well as the sources of genetic and environmental variation and covariation in element concentrations. We evaluated the chromosomal locations of genes affecting these characteristics by linkage analysis in 501 dizygotic twin pairs., Results: Concentrations of Cu, Se, and Zn, and of As and Hg showed substantial correlations, concentrations of As and Hg due mainly to common genetic effects. Genetic linkage analysis showed significant linkage for Pb [chromosome 3, near SLC4A7 (solute carrier family 4, sodium bicarbonate cotransporter, member 7)] and suggestive linkage for Cd (chromosomes 2, 18, 20, and X), Hg (chromosome 5), Se (chromosomes 4 and 8), and Zn {chromosome 2, near SLC11A1 [solute carrier family 11 (proton-coupled divalent metal ion transporters)]}., Conclusions: Although environmental exposure is a precondition for accumulation of toxic elements, individual characteristics and genetic factors are also important. Identification of the contributory genetic polymorphisms will improve our understanding of trace and toxic element uptake and distribution mechanisms.

In the current study, two hypotheses about the role of harsh discipline (HD) in explaining the sex difference in the prevalence of conduct disorder (CD) were evaluated: that boys exhibit more CD than girls because (1) they are exposed to more HD and/or (2) there is a greater association between HD and CD in boys. These hypotheses were evaluated in a sample of male and female adult twins from different families (N = 3,502) as well as a sample of adult twin brothers and sisters (N = 655) in order to examine the extent to which sex differences remained after controlling for between-family differences. Retrospective reports of HD experienced between ages 6-13 and DSM-IV CD symptoms experienced before age 18 were obtained via structured psychiatric telephone interviews. Boys reported higher mean levels of HD and CD than girls, both between and within families, and the results of model-fitting analyses suggested that differences in the use of harsh disciplinary practices for sons versus daughters may partially explain the sex difference in the prevalence of CD. Between families, the relation between HD and CD was greater for girls than boys, but within families, there was no evidence of a sex difference in the relation between HD and CD. Inconsistent between-family and within-family results suggest that factors that differ between families are confounded with sex differences in the relation between HD and CD. A more stringent test of sex differences involves eliminating these between-family differences by studying boys and girls within the same family.

The extended twin kinship design allows the simultaneous testing of additive and nonadditive genetic, shared and individual-specific environmental factors, as well as sex differences in the expression of genes and environment in the presence of assortative mating and combined genetic and cultural transmission (Eaves et al., 1999). It also handles the contribution of these sources of variance to the (co)variation of multiple phenotypes. Keller et al. (2008) extended this comprehensive model for family resemblance to allow or a flexible specification of assortment and vertical transmission. As such, it provides a general framework which can easily be reduced to fit subsets of data such as twin-parent data, children-of-twins data, etc. A flexible Mx specification of this model that allows handling of these various designs is presented in detail and applied to data from the Virginia 30,000. Data on height, body mass index, smoking status, church attendance, and political affiliation were obtained from twins and their families. Results indicate that biases in the estimation of variance components depend both on the types of relative available for analysis, and on the underlying genetic and environmental architecture of the phenotype of interest.

Alcohol dependence symptoms and consumption measures were examined for stability and heritability. Data were collected from 12,045 individuals (5376 twin pairs, 1293 single twins) aged 19 to 90 years in telephone interviews conducted in three collection phases. Phases 1 and 2 were independent samples, but Phase 3 targeted families of smokers and drinkers from the Phase 1 and 2 samples. The stability of dependence symptoms and consumption was examined for 1158 individuals interviewed in both Phases 1 and 3 (mean interval = 11.0 years). For 1818 individuals interviewed in Phases 2 and 3 (mean interval = 5.5 years) the stability of consumption was examined. Heritability was examined for each collection phase and retest samples from the selected Phase 3 collection. The measures examined were a dependence score, based on DSM-IIIR and DSM-IV criteria for substance dependence, and a quantity x frequency measure. Measures were moderately stable, with test-retest correlations ranging from .58 to .61 for dependence and from .55 to .64 for consumption. However, the pattern of changes over time for dependence suggested that the measure may more strongly reflect recent than lifetime experience. Similar to previous findings, heritabilities ranged from .42 to .51 for dependence and from .31 to .51 for consumption. Consumption was significantly less heritable in the younger Phase 2 cohort (23-39 years) compared to the older Phase 1 cohort (28-90 years).

Cigarette smoking during pregnancy (CSDP) is associated with a number of negative outcomes in the offspring. Therefore, clarifying the correlates of CSDP and the extent to which CSDP is associated with nicotine dependence is an important step toward reducing its rate in the general population. Using data from 1,134 adult Australian female monozygotic and dizygotic twin pairs, we explored the associations between CSDP and sociodemographic and psychiatric correlates and between CSDP and patterns of cigarette smoking. Further, we examined the role of heritable and environmental influences on CSDP and investigated whether these latent risk factors are shared with a predisposition to nicotine dependence. Women smoking during an entire pregnancy reported heavier dependence and more unsuccessful quit attempts, compared with the community sample of mothers and with women who smoked during only part of a pregnancy. Educational attainment, weekly church attendance, spousal current smoking, and nicotine dependence also were associated with CSDP. Heritable influences explained 34% of the variation in CSDP, with the remainder related to nonshared environmental factors. A large proportion of the genetic influences on CSDP were shared with DSM-III-R nicotine dependence, with little overlap across the nonshared environmental influences. A lifetime history of difficulty with smoking cessation, in conjunction with social background and psychiatric comorbidity, especially during pregnancy, needs to be considered by treatment providers when counseling expectant mothers about the potential risks of CSDP.

Background: Lead is an environmental pollutant that causes acute and chronic toxicity. Surveys have related mean blood lead concentrations to exogenous sources, including industrial activity, use of lead-based paints, or traffic density. However, there has been little investigation of individual differences in lead absorption, distribution, or toxicity, or of genetic causes of such variation., Objectives: We assessed the genetic contribution to variation in blood lead concentration in adults and conducted a preliminary search for genes producing such variation., Methods: Erythrocyte lead concentration was measured by inductively coupled plasma mass spectrometry in venous blood samples from 2,926 Australian adult male and female twins. Mean lead concentrations were compared by place of residence, social class and education, and by the subjects' age, sex, alcohol intake, smoking habits, iron status, and HFE genotype., Results: After adjustment for these covariates, there was strong evidence of genetic effects but not for shared environmental effects persisting into adult life. Linkage analysis showed suggestive evidence (logarithm of odds = 2.63, genome-wide p = 0.170) for a quantitative trait locus affecting blood lead values on chromosome 3 with the linkage peak close to SLC4A7, a gene whose product affects lead transport., Conclusions: We conclude that genetic variation plays a significant role in determining lead absorption, lead distribution within the body, or both.

Background: This study examined the relationships between self-reported childhood sexual abuse (CSA) and drug-related outcomes in an Australian twin panel., Method: A semi-structured psychiatric interview was conducted in 1996-2000 by telephone with young adult Australian twins (mean age 29.9 years). Data reported here are from 6050 twins who responded to both CSA and drug-related items., Results: A history of CSA was associated with significant risk for subsequently occurring regular smoking and use of each illicit drug class. Further CSA-associated risk was found among regular users, for nicotine and alcohol dependence, and among illicit drug users, for abuse/dependence of most drug classes. In same-sex discordant pairs, significant risk for regular smoking and illicit drug use was found in twins with a history of CSA compared to their non-abused co-twins. Similar analyses for abuse/dependence found significant risk for opioids, any illicit drug, and any non-cannabis illicit drug. CSA was associated with significantly earlier drug use. Despite the association of CSA with risk for early-onset cannabis use and regular smoking, risks for illicit drug outcomes associated with CSA and with either form of early-onset use combine in near-additive fashion., Conclusions: CSA is associated with risk for subsequently occurring regular smoking and illicit drug use and abuse/dependence. Risks for drug use are mildly attenuated with control for familial contributions; similar risks for abuse/dependence remain significant for opioids and for illicit drugs combined across classes. Although we found evidence of earlier onset drug use with CSA, risks associated with CSA and with early-onset use combine in a largely additive manner.

Background: Children of alcoholics are significantly more likely to experience high-risk environmental exposures, including prenatal substance exposure, and are more likely to exhibit externalizing problems [e.g. attention deficit hyperactivity disorder (ADHD)]. While there is evidence that genetic influences and prenatal nicotine and/or alcohol exposure play separate roles in determining risk of ADHD, little has been done on determining the joint roles that genetic risk associated with maternal alcohol use disorder (AUD) and prenatal risk factors play in determining risk of ADHD., Method: Using a children-of-twins design, diagnostic telephone interview data from high-risk families (female monozygotic and dizygotic twins concordant or discordant for AUD as parents) and control families targeted from a large Australian twin cohort were analyzed using logistic regression models., Results: Offspring of twins with a history of AUD, as well as offspring of non-AUD monozygotic twins whose co-twin had AUD, were significantly more likely to exhibit ADHD than offspring of controls. This pattern is consistent with a genetic explanation for the association between maternal AUD and increased offspring risk of ADHD. Adjustment for prenatal smoking, which remained significantly predictive, did not remove the significant genetic association between maternal AUD and offspring ADHD., Conclusions: While maternal smoking during pregnancy probably contributes to the association between maternal AUD and offspring ADHD risk, the evidence for a significant genetic correlation suggests: (i) pleiotropic genetic effects, with some genes that influence risk of AUD also influencing vulnerability to ADHD; or (ii) ADHD is a direct risk-factor for AUD.

Objective: Using an offspring-of-twins design, we tested the hypothesis that exposure to paternal alcoholism during the child's first 12 years will increase offspring risk for subsequent alcohol-use disorders (AUD)., Method: Structured psychiatric interviews assessed history of psychiatric and substance-use disorders in Vietnam Era Twin Registry fathers (n = 512), their offspring (n = 877), and mothers of the offspring (n = 507). Exposure was defined as the fathers' endorsement of any Diagnostic and Statistical Manual of Mental Disorders (DSM), Fourth Edition, AUD symptom, according to the Lifetime Drinking History assessment (administered in 1999), at any time between off- spring ages 0-12 years; all fathers had satisfied DSM, Third Edition, Revised (DSM-III-R), criteria for alcohol dependence in a 1992 diagnostic interview. Cox proportional hazards models were fit to predict time to first symptom of abuse/dependence in offspring., Results: Off- spring exposed to paternal alcoholism were significantly more likely to develop an AUD when compared with offspring of nonalcoholic fathers (hazard ratio [HR] = 1.51; 95% confidence interval [CI]: 1.10-2.07). Although offspring unexposed to paternal alcoholism did not significantly differ from control offspring (HR = 1.50, 95% CI: 0.93-2.41), the magnitude of association was similar to that in the exposed offspring. There were no significant differences in AUD between offspring of alcoholics who were exposed and those who were not exposed to paternal alcoholism, as long as fathers had satisfied DSM-III-R criteria for alcohol dependence at some point in their lives., Conclusions: There does not appear to be a relationship between exposure to paternal alcoholism during childhood and development of an AUD in offspring. Genetic and high-risk environmental factors that are correlated with lifetime paternal alcoholism may be stronger predictors of offspring AUD than fathers' problem drinking. Future research should be encouraged, using more comprehensive analyses, to examine the role of family genetic influences and other family environmental influences on offspring alcohol outcomes.

Background: The objective was to determine whether the pattern of environmental and genetic influences on deviant personality scores differs from that observed for the normative range of personality, comparing results in adolescent and adult female twins., Methods: A sample of 2,796 female adolescent twins ascertained from birth records provided Junior Eysenck Personality Questionnaire data. The average age of the sample was 17.0 years (S.D. 2.3). Genetic analyses of continuous and extreme personality scores were conducted. Results were compared for 3,178 adult female twins., Results: Genetic analysis of continuous traits in adolescent female twins were similar to findings in adult female twins, with genetic influences accounting for between 37% and 44% of the variance in Extraversion (Ex), Neuroticism (N), and Social Non-Conformity (SNC), with significant evidence of shared environmental influences (19%) found only for SNC in the adult female twins. Analyses of extreme personality characteristics, defined categorically, in the adolescent data and replicated in the adult female data, yielded estimates for high N and high SNC that deviated substantially (p < .05) from those obtained in the continuous trait analyses, and provided suggestive evidence that shared family environment may play a more important role in determining personality deviance than has been previously found when personality is viewed continuously. However, multiple-threshold models that assumed the same genetic and environmental determinants of both normative range variation and extreme scores gave acceptable fits for each personality dimension., Conclusions: The hypothesis of differences in genetic or environmental factors responsible for N and SNC among female twins with scores in the extreme versus normative ranges was partially supported, but not for Ex.

This article applies methods of latent class analysis (LCA) to data on lifetime illicit drug use in order to determine whether qualitatively distinct classes of illicit drug users can be identified. Self-report data on lifetime illicit drug use (cannabis, stimulants, hallucinogens, sedatives, inhalants, cocaine, opioids and solvents) collected from a sample of 6265 Australian twins (average age 30 years) were analyzed using LCA. Rates of childhood sexual and physical abuse, lifetime alcohol and tobacco dependence, symptoms of illicit drug abuse/dependence and psychiatric comorbidity were compared across classes using multinomial logistic regression. LCA identified a 5-class model: Class 1 (68.5%) had low risks of the use of all drugs except cannabis; Class 2 (17.8%) had moderate risks of the use of all drugs; Class 3 (6.6%) had high rates of cocaine, other stimulant and hallucinogen use but lower risks for the use of sedatives or opioids. Conversely, Class 4 (3.0%) had relatively low risks of cocaine, other stimulant or hallucinogen use but high rates of sedative and opioid use. Finally, Class 5 (4.2%) had uniformly high probabilities for the use of all drugs. Rates of psychiatric comorbidity were highest in the polydrug class although the sedative/opioid class had elevated rates of depression/suicidal behaviors and exposure to childhood abuse. Aggregation of population-level data may obscure important subgroup differences in patterns of illicit drug use and psychiatric comorbidity. Further exploration of a 'self-medicating' subgroup is needed.

Research suggests that frontal EEG asymmetry (FA) is a relatively stable trait associated with individual differences in dispositional affect (affective style) and liability to mood disorders. If FA is genetically determined, it can potentially serve as an endophenotype in genetic studies of temperament and mood disorders. The purpose of this study was to assess heritability of FA as well as alpha band EEG power measured at different frontal recording sites. Resting EEG data from a population-based sample of 246 young adult female twins including 73 monozygotic (MZ) and 50 dizygotic (DZ) pairs were analyzed using linear structural equation modeling. FA measured at mid-frontal locations (F3 and F4) showed low but significant heritability, suggesting that 27% of the observed variance can be accounted for by genetic factors. There was no evidence for genetic influences on FA measured at lateral-frontal (F7 and F8) locations. In contrast, alpha band power was highly heritable at all four frontal sites (85-87%). These findings suggest that: (1) genetic influences on FA are very modest and therefore FA has a limited utility as an endophenotype for genetic studies of mood disorders and (2) prefrontal neural circuitry underlying individual differences in affective style is characterized by high developmental plasticity.

Aims: To investigate the role of measured risk factors and the influence of genetic and environmental factors on regular cigarette smoking. Design Members of monozygotic and dizygotic, including unlike-sex twin pairs (n = 6257) from a young adult cohort from the Australian Twin Registry., Methods: Cox proportional hazards models were used to determine whether putative risk factors were significantly associated with regular cigarette smoking. Risk factors were classified into four tiers: tier 1 (parental history, including parental education, alcoholism and cigarette smoking), tier 2 (early home and family influences), tier 3 (early life events, e.g. trauma) and tier 4 (psychiatric symptoms/disorders with onset prior to 14 years), after controlling for gender, zygosity and their interactions. Genetic models were fitted to examine the heritability of smoking behavior before and after controlling for significant covariates from the four tiers., Findings: Parental history of cigarette smoking and alcoholism, parental closeness and home environment, as well as incidence of childhood sexual abuse or other trauma, a history of early onset panic attacks and conduct problems were associated with regular cigarette smoking. Important age interactions were found, particularly for family background risk factors. Regular cigarette smoking was moderately heritable, even after accounting for significant covariates., Conclusions: Several measured risk factors are associated with regular smoking. While some of the genetic influences on regular smoking may be shared with these risk factors, a significant proportion of the genetic vulnerability to regular smoking is phenotype-specific.

Background: Causes of variation in cardiovascular risk factors include biological variation within individuals, and more permanent differences between individuals, which are at least partly genetic in origin. We have compared the magnitude of genetic and non-genetic factors within and across occasions through repeated measures of plasma cholesterol in twin subjects, and have also determined how far the same genes affect cholesterol levels at different ages., Methods: Data on plasma total cholesterol were extracted for 208 twin pairs who had provided blood on up to six occasions across a period of 17 years. They were aged 18-30 years at the time of first study and 30-47 at the time of the last. Multivariate models of variation due to genetic, shared environmental and unique environmental factors were fitted to the multi-occasion data and the proportions of variation due to these factors were estimated., Results: One genetic factor influenced plasma cholesterol on all occasions and a second genetic factor only influenced cholesterol results on the fifth and sixth occasions 10-17 years after the first. Environmental factors did not have significant long-term effects., Conclusions: We conclude that individuals' long-term mean plasma cholesterol values are strongly genetically determined, but that some of these genes are age-specific in their effects.

Background: Genetic influences have been shown to play a major role in determining the risk of attention-deficit hyperactivity disorder (ADHD). In addition, prenatal exposure to nicotine and/or alcohol has also been suggested to increase risk of the disorder. Little attention, however, has been directed to investigating the roles of genetic transmission and prenatal exposure simultaneously., Method: Diagnostic telephone interview data from parents of Missouri adolescent female twin pairs born during 1975-1985 were analyzed. Logistic regression models were fitted to interview data from a total of 1936 twin pairs (1091 MZ and 845 DZ pairs) to determine the relative contributions of parental smoking and drinking behavior (both during and outside of pregnancy) as risk factors for DSM-IV ADHD. Structural equation models were fitted to determine the extent of residual genetic and environmental influences on ADHD risk while controlling for effects of prenatal and parental predictors on risk., Results: ADHD was more likely to be diagnosed in girls whose mothers or fathers were alcohol dependent, whose mothers reported heavy alcohol use during pregnancy, and in those with low birth weight. Controlling for other risk factors, risk was not significantly increased in those whose mothers smoked during pregnancy. After allowing for effects of prenatal and childhood predictors, 86% of the residual variance in ADHD risk was attributable to genetic effects and 14% to non-shared environmental influences., Conclusions: Prenatal and parental risk factors may not be important mediators of influences on risk with much of the association between these variables and ADHD appearing to be indirect.

Introduction: In substance abusing families, sources of familial comorbidity are potentially confounded by genetic-environmental (GE) interplays. The children-of-twins (COT) design can be used to elucidate the association of a parental trait and an offspring outcome such as the association of parental alcoholism and offspring suicidality., Methods: We examined the association of paternal alcoholism and offspring suicidal behaviors in an adolescent and young adult COT sample of 'Vietnam Era Twins' offspring who had completed an interview including a comprehensive assessment of lifetime suicidal behaviors. We stratified the COT sample into four groups contingent upon paternal zygosity, MZ versus DZ, and lifetime paternal alcohol dependence history (AD), positive versus negative. We examined whether the relationship of paternal alcoholism and offspring suicidality was best explained by genetic predispositions common to alcoholism and suicidality or by GE interplay--environmental influences correlated with parental alcoholism or the interaction of genetic and environmental factors., Results: Our results suggest a main effect of paternal alcoholism on offspring suicide attempt; COT analyses do not support a purely genetic explanation for this association., Discussion: Suicide attempts probably result from GE interplays and must be studied in genetically informative samples of offspring of substance abusing parents.

This study provides findings to assist in identifying factors that contribute to the current clinical and public health debate of the obesity epidemic. The study examined the genetics of adult-onset weight change in middle-aged male-male twins controlling for weight in early adulthood, lifetime history of tobacco use and alcohol dependence, and aimed to estimate the proportion of genetic factors that influence weight change between early adulthood and middle age in white middle-class males. The study was a classic longitudinal twin design and used Body Mass Index (BMI) for three waves of data collection from the Vietnam Era Twin Registry--induction physicals (approximately 1968), 1987 and 1990--or periods corresponding between young adulthood and middle age. Univariate heritability estimates for BMI at all three data periods were conducted as well as a Cholesky longitudinal genetic analysis for weight change controlling for BMI at military induction, smoking and alcohol use. Frequency data indicated that the sample was on average classified as normal BMI in their 20s; but BMI gradually increased during the next twenty years. Univariate data for each data period indicated that additive genetic factors accounted for between 63% and 69% of total variance in BMI. The Cholesky longitudinal genetic analysis of BMI87 and BMI90, controlling for BMI at military induction, indicated that more than half of the change in BMI from early adulthood to middle age remains heritable. No shared environmental factors were identified, thus the remainder of the variance was accounted for by nonshared, or unique, environmental factors and error. The data analysis suggests that treatments and public health interventions need to recognize the magnitude of genetic factors if short-term and long-term interventions are to be effective.

The association of college attendance with alcohol use and alcohol use disorders was examined in a population-based young adult female twin sample identified from a systematic search of birth records. College-attending women consumed a larger overall volume of alcohol than did their non-college-attending peers, but they were not more likely to be diagnosed with an alcohol use disorder. Significant associations between college attendance and alcohol involvement were probed using 3 different complementary research designs: multivariate cross-sectional analyses, longitudinal analyses of the precollege and college years, and cotwin-control analyses of twin pairs discordant for attending college. Although demographic and lifestyle characteristics accounted for most or all of the association between college attendance and alcohol involvement, there was 1 aspect of drinking behavior, occasionally consuming large quantities of alcohol, that remained significantly associated with college attendance even after controlling for these characteristics or for genetic and family background factors. These results are consistent with the conclusion that some aspect of the college experience may be an important environmental risk factor for this pattern of drinking among young adults., (Copyright 2004 APA.)

Background: Because alcohol has multiple dose-dependent consequences, it is important to understand the causes of individual variation in the amount of alcohol used. The aims of this study were to assess the long-term repeatability and genetic or environmental causes of variation in alcohol intake and to estimate the degree of overlap with causes of susceptibility to alcohol dependence., Methods: Data were used from three studies conducted between 1980 and 1995 on volunteer adult male and female Australian twin subjects. In each study, alcohol intake was reported both as quantity x frequency and as past-week data. Repeatability was calculated as correlations between occasions and between measures, and the effects of genes and environment were estimated by multivariate model fitting to the twin pair repeated measures of alcohol use. Relationships between mean alcohol use and the lifetime history of DSM-III-R alcohol dependence were tested by bivariate model fitting., Results: Repeatability of the alcohol intake measures was between 0.54 and 0.85, with the highest repeatability between measures within study and the lowest repeatability between the first and last studies. Reported alcohol consumption was mainly affected by genetic factors affecting all times of study and by nonshared environmental factors (including measurement error) unique to each time of study. Genes that affect alcohol intake do affect alcohol dependence, but genetic effects unique to dependence are also significant; environmental effects are largely unique to either intake and dependence., Conclusions: Nearly all the repeatable component of variation in alcohol intake is due to genetic effects. Genes affecting intake also affect dependence risk, but there are other genes that affect dependence alone. Studies aiming to identify genes that affect alcohol use disorders need to test loci and candidate genes against both phenotypes., (Copyright 2004 Research Society on Alcoholism)

The authors examined genetic and environmental influences, including the contributions of 2 measured aspects of the shared environment of twins (paternal absence, socioeconomic disadvantage) on the development of mother-reported separation anxiety disorder (SAD) history in a sample of 1,887 female twin pairs. Four different symptom categories of SAD were considered. Results revealed that all 4 SAD symptom categories were significantly heritable, whereas the contribution of shared environmental influences to the variation in risk was significant for only 2 of the 4 SAD categories. Paternal absence was found to have an important influence in vulnerability for SAD, whereas the effect of socioeconomic disadvantage was less robust. Evidence for race differences in the etiology of SAD was not found.

The objective of this study was to determine if mothers' retrospective reports about events in their pregnancies with twins are reliable and stable. Six hundred and twenty-four mothers completed psychiatric interviews about their twins. These interviews also contained questions about the mothers' pregnancies, the perinatal period, and the child's early development. The mothers reported first on one twin and then on the other with interviews spaced from 3 days to 2 weeks apart. Thus mothers reported on the same pregnancy twice. Of these mothers, 47 were re-interviewed 6 to 18 months later by raters blind to the results of the initial interview. The twin design allowed us to compare the short-term reliability of the 624 mothers' reports of the same pregnancy. The re-interview of the 47 mothers enabled us to compare the stability of reports over a longer time period. Agreement between the reports was measured with the kappa statistic. Kappas were good to excellent for the short-term reports of pregnancy for each twin for the 624 mothers. Kappas were equally high for the 47 mothers that were re-interviewed 6 to 18 months later. Mothers show good reliability and stability of reporting about events during pregnancy.

Objective: To estimate genetic, environmental, and rater contrast influences on parental reports of Activities, Social, School, and Total Competence scales of the Child Behavior Checklist (CBCL)., Method: Parents of 492 twin pairs aged 8-12 years completed CBCLs. Genetic, shared and unique environmental, and rater bias effects were estimated for the Activities, Social, School, and Total Competence scales. Data on boys and girls were analyzed separately., Results: Moderate genetic influences were found only for the School scale (60%-76%), while shared environment accounted for most of the variance in Activities, Social, and Total Competence scales. Gender differences are reported. Similar to a prior twin study of CBCL problem syndromes, there was no evidence of rater bias., Conclusions: Estimates of genetic influence on these child competence domains were high for School Competence, while social competence and activity competence evidenced higher levels of shared environmental influences. Organization and wording of CBCL items may avoid rater biases in reporting. These findings have implications for interventions to improve school, social, and activities competence.

Alcohol expectancies are an important proximal causal risk factor in several models of the familial transmission of alcohol use, abuse, and dependence, yet the familial transmission of alcohol expectancies is not well understood. The purpose of this study was to examine the familial transmission of positive alcohol expectancies. Participants were 2,627 14- to 22-year-old female twins. Experiences shared by twins, rather than genetic factors, explained most of the familial similarity for positive alcohol expectancies, but an even larger proportion of the variation in positive alcohol expectancies was explained by nonfamilial factors. The extent to which the familial similarity for positive alcohol expectancies was moderated by age, race, drinking status, and the sharing of peer groups was also examined.

Objective: Despite the general use of DSM-IV attention-deficit/hyperactivity disorder (ADHD) subtypes, there is controversy over the optimal phenotyping strategy for this disorder.This report contrasts two ADHD subtyping approaches on the prediction of cognitive function and educational achievement., Method: ADHD subtypes were determined using DSM-IV and latent class approaches for a population sample of 1,154 child and adolescent twins using parent report data. Twins completed cognitive and achievement testing and parents reported on school grades, special education placement, and history of being held back in school., Results: The DSM-IV primarily inattentive and combined subtype ADHD groups showed significant deficits in cognitive and achievement testing, worse grades, and increased use of special education resources compared with the primarily hyperactive/impulsive subtype and no-ADHD groups. Clinically relevant and less severe latent class ADHD subtypes were also associated with deficits in cognitive and achievement testing, grades, and special education use., Conclusions: DSM-IV primarily inattentive and combined subtypes of ADHD have similar significant patterns of cognitive and academic dysfunction in the general population. Latent class-defined ADHD subtypes also have patterns of serious cognitive and achievement deficits.

Female twin pairs were identified from birth records, and their families invited to participate in a prospective study of the determinants of alcohol problems in women. We investigated sampling biases arising because of failure to locate families, or non-cooperation of families. Out of 2644 families with a live-born pair (born between July 1975 and December 1986) who survived beyond infancy, contact was established and a brief screening interview completed with 90% (N = 2380). Fewer than 6% of located families declined to participate in the initial screening interview. Predictors of failure to locate a family or to obtain a screening interview were identified from information recorded in birth records, and from neighborhood characteristics identified from 1990 US Census block group data for the family residence when the twins were born. African-American families were under-represented in the final sample, but this effect was barely significant when other variables were controlled for. Under-represented were families where the mother was 19 or younger at the birth of the twins, where the mother herself was born out-of-state, or where information about biological father was not reported in the birth record. Non-participating families on average came from neighborhoods with a higher proportion of residents living in poverty, and with a higher proportion of African-American residents. Sampling biases were however small. The unusual cooperativeness in research of families with twins persists.

Genetic research on risk of alcohol, tobacco or drug dependence must make allowance for the partial overlap of risk-factors for initiation of use, and risk-factors for dependence or other outcomes in users. Except in the extreme cases where genetic and environmental risk-factors for initiation and dependence overlap completely or are uncorrelated, there is no consensus about how best to estimate the magnitude of genetic or environmental correlations between Initiation and Dependence in twin and family data. We explore by computer simulation the biases to estimates of genetic and environmental parameters caused by model misspecification when Initiation can only be defined as a binary variable. For plausible simulated parameter values, the two-stage genetic models that we consider yield estimates of genetic and environmental variances for Dependence that, although biased, are not very discrepant from the true values. However, estimates of genetic (or environmental) correlations between Initiation and Dependence may be seriously biased, and may differ markedly under different two-stage models. Such estimates may have little credibility unless external data favor selection of one particular model. These problems can be avoided if Initiation can be assessed as a multiple-category variable (e.g. never versus early-onset versus later onset user), with at least two categories measurable in users at risk for dependence. Under these conditions, under certain distributional assumptions, recovery of simulated genetic and environmental correlations becomes possible. Illustrative application of the model to Australian twin data on smoking confirmed substantial heritability of smoking persistence (42%) with minimal overlap with genetic influences on initiation.

Objective: To provide an overview of the genetic epidemiology of substance use and misuse in adolescents. Method: A selective review of genetically informative research strategies, their limitations, and key findings examining issues related to the heritability of substance use and substance use disorders in children and adolescents is presented. Results: Adoption, twin, and extended-family designs have established there is a strong heritable component to liability to nicotine, alcohol, and illicit drug dependence in adults. However, shared environmental influences are relatively stronger in youth samples and at earlier stages of substance involvement (e.g., use). There is considerable overlap in the genetic influences associated with the abuse/dependence across drug classes, and shared genetic influences contribute to the commonly observed associations between substance-use disorders and externalizing and, to a lesser extent, internalizing psychopathology. Rapid technologic advances have made the identification of specific gene variants that influence risks for substance-use disorders feasible, and linkage and association (including genomewide association studies) have identified promising candidate genes implicated in the development of substance-use disorders. Conclusions: Studies using genetically informative research designs, including those that examine aggregate genetic factors and those examining specific gene variants, individually and in interaction with environmental influences, offer promising avenues not only for delineating genetic effects on substance-use disorders but also for understanding the unfolding of risk across development and the interaction between environmental and genetic factors in the etiology of these disorders. (Contains 2 figures.)