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Association Between Copy Number Variation Losses and Alcohol Dependence Across A frican A merican and E uropean A merican Ethnic Groups
Author(s) -
Ulloa Alvaro E.,
Chen Jiayu,
Vergara Victor M.,
Calhoun Vince,
Liu Jingyu
Publication year - 2014
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.12364
Subject(s) - copy number variation , genetics , biology , gene , genome
Background Copy number variations ( CNV s) are structural genetic mutations consisting of segmental gains or losses in DNA sequence. Although CNV s contribute substantially to genomic variation, few genetic and imaging studies report association of CNV s with alcohol dependence ( AD ). Our purpose is to find evidence of this association across ethnic populations and genders. This work is the first AD – CNV study across ethnic groups and the first to include the A frican A merican (AA) population. Methods This study considers 2 CNV data sets, one for discovery (2,345 samples) and the other for validation (239 samples), both including subjects with AD and healthy controls of E uropean and A frican ancestry. Our analysis assesses the association between AD and CNV losses across ethnic groups and gender by examining the effect of overall losses across the whole genome, collective losses within individual cytogenetic bands, and specific losses in CNV regions. Results Results from the discovery data set showed an association between CNV losses within 16q12.2 and AD diagnosis ( p = 4.53 × 10 −3 ). An overlapping CNV region from the validation data set exhibited the same direction of effect with respect to AD ( p = 0.051). This CNV region affects the genes CES 1p1 and CES 1, which are members of the carboxylesterase ( CES ) family. The enzyme encoded by CES 1 is a major liver enzyme that typically catalyzes the decomposition of ester into alcohol and carboxylic acid and is involved in drug or xenobiotics, fatty acid, and cholesterol metabolisms. In addition, the most significantly associated CNV region was located at 9p21.2 ( p = 1.9 × 10 −3 ) in our discovery data set. Although not observed in the validation data set, probably due to small sample size, this result might hold potential connection to AD given its connection with neuronal death. In contrast, we did not find any association between AD and the overall total losses or the collective losses within individual cytogenetic bands. Conclusions Overall, our study provides evidence that the specific CNV s at 16q12.2 contribute to the development of alcoholism in AA and E uropean A merican populations.