Deviant Peer Affiliation and Antisocial Behavior: Interaction with Monoamine Oxidase A (MAOA) Genotype

Although genetic and environmental factors are separately implicated in the development of antisocial behavior (ASB), interactive models have emerged relatively recently, particularly those incorporating molecular genetic data. Using a large sample of male Caucasian adolescents and young adults from the National Longitudinal Study of Adolescent Health (Add Health), the association of deviant peer affiliation, the 30-base pair variable number tandem repeat polymorphism in promoter region of the monoamine oxidase-A (MAOA) gene, and their interaction, with antisocial behavior (ASB) was investigated. Weighted analyses accounting for over-sampling and clustering within schools as well as controlling for age and wave suggested that deviant peer affiliation and MAOA genotype were each significantly associated with levels of overt ASB across a 6-year period. Only deviant peer affiliation was significantly related to covert ASB, however. Additionally, there was evidence suggestive of a gene-environment interaction (G × E) where the influence of deviant peer affiliation on overt ASB was significantly stronger among individuals with the high-activity MAOA genotype than the low-activity genotype. MAOA was not significantly associated with deviant peer affiliation, thus strengthening the inference of G × E rather than gene-environment correlation (rGE). Different forms of gene-environment interplay and implications for future research on ASB are discussed

Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium

BACKGROUND Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC. METHODS Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals). RESULTS Positive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation. CONCLUSION This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts

The risk for drug abuse, alcohol use disorder, and psychosocial dysfunction in offspring from high-density pedigrees : its moderation by personal, family, and community factors

Previous high-risk family designs in psychiatry have focused largely on offspring of affected parents. We take a pedigree-based approach and examine the social, psychological, and psychiatric features of offspring from extended pedigrees selected for high-densities of alcohol use disorder (AUD) or drug abuse (DA). We identified, from the Swedish population, 665,715 pedigrees containing a mean of 17.9 parents, aunts/uncles, grandparents, and cousins of a core full-sibship we term the pedigree offspring. We then derived 13 empirical classes of these pedigrees based on the density of cases of AUD and DA. High rates of AUD or DA in the pedigrees were associated in the offspring with lower levels of school achievement, educational attainment, and resilience, and higher rates of psychiatric illness, neighborhood deprivation, unemployment, social welfare, early retirement, and criminal convictions. Effect sizes were large in the offspring of the highest density pedigrees and were stronger in high-density DA than in high-density AUD pedigrees. Sensitivity to the pathogenic effects of membership in these high-risk sibships was substantially attenuated by high levels of school attainment and resilience, female sex, and absence of parental divorce. Offspring of pedigrees with a high density of AUD or DA are multiply disadvantaged and typically suffer from educational difficulties, social deprivation, socio-economic dysfunction, personality problems, and elevated rates of both psychiatric disorders and externalizing syndromes. Despite these difficulties, personal strengths, including improved school achievement and resilience, and an intact parental marriage can substantially buffer these adverse effects and might form a basis for prevention efforts