The joint effects of ADH1B variants and childhood adversity on alcohol related phenotypes in African-American and European-American women and men.
- Authors
- Sartor, Carolyn E; Wang, Zuoheng; Xu, Ke; Kranzler, Henry R; Gelernter, Joel
- Year
- 2014
- Journal
- Alcoholism, clinical and experimental research
- PMID
- 25410943
- DOI
- 10.1111/acer.12572
- PMCID
- PMC4445128
BACKGROUND: The ADH1B gene has consistently been implicated in problem drinking, but rarely incorporated into gene by environment investigations of alcohol phenotypes. This study examined the joint effects of variation in ADH1B and childhood adversity-a well-documented risk factor for alcohol problems and moderator of genetic liability to psychiatric outcomes-on maximum drinks consumed in a 24-hour period (maxdrinks) and alcohol use disorder (AUD) symptoms. METHODS: Data were drawn from 2,617 African-American (AA) and 1,436 European-American (EA) participants (42% female) in a multisite genetic study of substance dependence. We tested the most significant ADH1B single nucleotide polymorphisms for alcohol dependence from a genomewide association study with this sample, ADH1B-rs1229984 (Arg48His) and ADH1B-rs2066702 (Arg370Cys), in EA and AA subsamples, respectively. RESULTS: Ordinal regression analyses conducted separately by sex and population revealed significant main effects for childhood adversity for both alcohol phenotypes in AA women and men and for maxdrinks in EA women. A significant rs1229984 by childhood adversity interaction was observed for AUD symptoms in EA men. Unexposed His-allele carriers reported a mean of 3.6 AUD criteria, but adversity-exposed His-allele carriers endorsed approximately the same number (6.3) as those without the protective allele (6.3 and 7.0 for adversity-exposed and -unexposed groups, respectively). CONCLUSIONS: Results suggest that under conditions of childhood adversity, the His allele does not exert its protective effects in EA men (OR = 0.57, CI: 0.32 to 1.01; p = 0.056). Findings highlight the robust risk effect conferred by childhood adversity and the importance of considering population and sex in genetically informative investigations of its association with alcohol outcomes.
Mean alcohol use disorder (AUD) symptoms in European-American men by ADH1B-rs1229984 genotype and childhood adversity status
LLM interpretation
This line graph shows the mean number of alcohol use disorder (AUD) criteria endorsed by European-American men, categorized by ADH1B-rs1229984 genotype (AA/AG vs. GG) and childhood adversity status (Unexposed vs. Exposed). The "Exposed" group shows higher mean AUD symptoms across both genotypes, with a more pronounced increase in symptoms for the "Unexposed" group when moving from the AA/AG to the GG genotype. Error bars are provided for each data point, but no p-values or significance markers are explicitly labeled.
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