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Associations Between Genomic Variants in Alcohol Dehydrogenase Genes and Alcohol Symptomatology in American Indians and European Americans: Distinctions and Convergence
Author(s) -
Peng Qian,
Gizer Ian R.,
Wilhelmsen Kirk C.,
Ehlers Cindy L.
Publication year - 2017
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13480
Subject(s) - alcohol dehydrogenase , genetics , convergence (economics) , gene , adh1b , alcohol , biology , enzyme , dehydrogenase , biochemistry , branched chain alpha keto acid dehydrogenase complex , economics , economic growth
Background Higher rates of alcohol use disorders ( AUD ) have been observed in some Native American populations than other ethnic groups such as European Americans ( EA s) in the United States. Previous studies have shown that variation in the alcohol dehydrogenase ( ADH ) genes may affect the risk for development of AUD and that the prevalence of these variants differs depending on the ancestral origins of a population. Methods In this study, we assessed sequencing variants in the ADH genomic region ( ADH 1‐7 ) and tested for their associations with AUD phenotypes in 2 independent populations: an American Indian ( AI ) community sample and an EA cohort from the San Francisco Family Alcohol Study. Association tests were conducted for both common and rare variants using sequencing data for 2 phenotypes: the number of alcohol‐related life events and the count of alcohol dependence drinking symptoms. A regularized regression method was used to select the best set of ADH variants associated with phenotypes. Variance component model was incorporated in all analyses to leverage the admixture and relatedness. Results Two variants near ADH 4 and 2 near ADH 1C exhibited significant associations with AUD in AI s; no variant was significant in EA s. Common risk variants in AI s were either absent from or much less frequent in EA s. The feature selection method selected mostly distinct yet often colocated subsets of ADH variants to be associated with AUD phenotypes between the 2 cohorts. In the rare‐variant analyses, the only association was observed between the whole region and the alcohol‐related life events in AI s. Conclusions Our results suggest that ADH variants, both common and rare, are more likely to impact risk for alcohol‐related symptomatology in this AI population than in this EA sample, and ADH variants that might affect AUD are likely different but convergent on similar regions between the 2 populations.