Liability to alcohol dependence (AD) is heritable, but little is known
about its complex polygenic architecture or its genetic relationship with other
disorders. To discover loci associated with AD and characterize the relationship
between AD and other psychiatric and behavioral outcomes, we carried out the
largest GWAS to date of DSM-IV diagnosed AD. Genome-wide data on 14,904
individuals with AD and 37,944 controls from 28 case/control and family-based
studies were meta-analyzed, stratified by genetic ancestry (European, N =
46,568; African; N = 6,280). Independent, genome-wide significant effects of
different ADH1B variants were identified in European
(rs1229984; p = 9.8E-13) and African ancestries (rs2066702; p = 2.2E-9).
Significant genetic correlations were observed with 17 phenotypes, including
schizophrenia, ADHD, depression, and use of cigarettes and cannabis. The genetic
underpinnings of AD only partially overlap with those for alcohol consumption,
underscoring the genetic distinction between pathological and non-pathological
drinking behaviors.
Previous reviews of the literature have suggested that shared environmental effects may be underestimated in adoption studies because adopted individuals are exposed to a restricted range of family environments. A sample of 409 adoptive and 208 non-adoptive families from the Sibling Interaction and Behavior Study (SIBS) was used to identify the environmental dimensions on which adoptive families show greatest restriction and to determine the effect of this restriction on estimates of the adoptive sibling correlation. Relative to non-adoptive families, adoptive families experienced a 41% reduction of variance in parent disinhibitory psychopathology and an 18% reduction of variance in socioeconomic status (SES). There was limited evidence for range restriction in exposure to bad peer models, parent depression, or family climate. However, restriction in range in parent disinhibitory psychopathology and family SES had no effect on adoptive-sibling correlations for delinquency, drug use, and IQ. These data support the use of adoption studies to obtain direct estimates of the importance of shared environmental effects on psychological development.
Moderate mean differences in quantitative indicators of mental health can lead to substantial differences in disorder prevalence. Although most adopted adolescents are psychologically healthy, they may be at elevated risk for some externalizing disorders, especially among those domestically placed.
We used a longitudinal twin design to examine the causal association between sexual, emotional, and physical abuse in childhood (before age 18) and borderline personality disorder (BPD) traits at age 24 using a discordant twin design and biometric modeling. Additionally, we examined the mediating and moderating effects of symptoms of childhood externalizing and internalizing disorders on the link between childhood abuse and BPD traits. Although childhood abuse, BPD traits, and internalizing and externalizing symptoms were all correlated, the discordant twin analyses and biometric modeling showed little to no evidence that consistent with a causal effect of childhood abuse on BPD traits. Instead, our results indicate that the association between childhood abuse and BPD traits stems from common genetic influences that, in some cases, also overlap with internalizing and externalizing disorders. These findings are inconsistent with the widely held assumption that childhood abuse causes BPD, and suggests that BPD traits in adulthood are better accounted for by heritable vulnerabilities to internalizing and externalizing disorders.
T he Enrichment Study (ES) was designed to extend the Minnesota Twin Family Study (MTFS)by oversampling 11-year-old twins at especially high risk for substance use disorders by virtue of having a childhood disruptive disorder. The sample was ascertained from Minnesota birth records. To identify high-risk twins, we conducted telephone screening interviews for parent-reported symptoms of attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) as well as indications of academic disengagement. Twins who exceeded a predetermined threshold were invited to participate. To facilitate comparison with the previously ascertained MTFS participants, a random sample of 11-year-old twins was also recruited. As part of the ES study, 499 twin pairs, and their parents, visited the University of Minnesota, where each participant completed a clinical interview, psychophysiological evaluation, and thorough assessment of environmental risk. We were highly successful in recruiting at-risk twins; 52% of the screened male twins and 41% of the screened females met criteria for a diagnosis of ADHD, CD, or oppositional defiant disorder (ODD). At the pair level, 63% of the screened pairs had at least one member with a childhood disruptive disorder. This article provides an overview of the study design and includes a review of recent findings using this sample of twins.
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