title: Childhood adversity moderates the effect of ADH1B on risk for alcohol-related phenotypes in Jewish Israeli drinkers.
abstract: Childhood adversity and genetic variant ADH1B-rs1229984 have each been shown to influence heavy alcohol consumption and disorders. However, little is known about how these factors jointly influence these outcomes. We assessed the main and additive interactive effects of childhood adversity (abuse, neglect and parental divorce) and the ADH1B-rs1229984 on the quantitative phenotypes 'maximum drinks in a day' (Maxdrinks) and DSM-Alcohol Use Disorder (AUD) severity, adjusting for demographic variables, in an Israeli sample of adult household residents (n = 1143) evaluated between 2007 and 2009. Childhood adversity and absence of the protective ADH1B-rs1229984 A allele were associated with greater mean Maxdrinks (mean differences: 1.50; 1.13, respectively) and AUD severity (mean ratios: 0.71; 0.27, respectively). In addition, childhood adversity moderated the ADH1B-rs1229984 effect on Maxdrinks (P < 0.01) and AUD severity (P < 0.05), in that there was a stronger effect of ADH1B-rs1229984 genotype on Maxdrinks and AUD severity among those who had experienced childhood adversity compared with those who had not. ADH1B-rs1229984 impacts alcohol metabolism. Therefore, among those at risk for greater consumption, e.g. those who experienced childhood adversity, ADH1B-rs1229984 appears to have a stronger effect on alcohol consumption and consequently on risk for AUD symptom severity. Evidence for the interaction of genetic vulnerability and early life adversity on alcohol-related phenotypes provides further insight into the complex relationships between genetic and environmental risk factors.
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
authors.forename: Jacquelyn L
authors.initials: JL
authors.lastname: Meyers
authors.forename: Dvora
authors.initials: D
authors.lastname: Shmulewitz
authors.forename: Melanie M
authors.initials: MM
authors.lastname: Wall
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Keyes
authors.forename: Efrat
authors.initials: E
authors.lastname: Aharonovich
authors.forename: Baruch
authors.initials: B
authors.lastname: Spivak
authors.forename: Abraham
authors.initials: A
authors.lastname: Weizman
authors.forename: Amos
authors.initials: A
authors.lastname: Frisch
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
authors.forename: Bridget F
authors.initials: BF
authors.lastname: Grant
authors.forename: Deborah
authors.initials: D
authors.lastname: Hasin
mesh_terms: D000328:Adult; D054523:Adult Survivors of Child Abuse / Q000523:psychology*; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000235:genetics* / Q000523:psychology; D019973:Alcohol-Related Disorders / Q000235:genetics* / Q000523:psychology; D000483:Alleles; D004243:Divorce / Q000523:psychology; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D007557:Israel; D007585:Jews / Q000235:genetics* / Q000523:psychology; D008297:Male; D008875:Middle Aged
chemical_list: C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase
keywords: ADH1B; Israel; alcohol consumption; alcohol use disorders; childhood adversity; interaction