Association Between Copy Number Variation Losses and Alcohol Dependence Across African American and European American Ethnic Groups. (11th February 2014)

• Record Type: Journal Article
• Authors: Ulloa, Alvaro E.; Chen, Jiayu; Vergara, Victor M.; Calhoun, Vince; Liu, Jingyu
• Is Part Of: Alcoholism. Volume 38:Number 5(2014:May)
• Page Start: 1266
• Page End: 1274
• Publication Date: 2014-02-11
• Subjects: Alcoholism -- Periodicals; Alcoholism -- Periodicals; Alcoolisme; Electronic journals; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.861005
• DOI: 10.1111/acer.12364
• Languages: English
• ISSNs: 0145-6008

Abstract

<abstract abstract-type="main" id="acer12364-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="acer12364-sec-0001" sec-type="section"> <title>Background</title> <p>Copy number variations (CNVs) are structural genetic mutations consisting of segmental gains or losses in DNA sequence. Although CNVs contribute substantially to genomic variation, few genetic and imaging studies report association of CNVs 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 African American (AA) population.</p> </sec> <sec id="acer12364-sec-0002" sec-type="section"> <title>Methods</title> <p>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 European and African 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.</p> </sec> <sec id="acer12364-sec-0003" sec-type="section"> <title>Results</title> <p>Results from the discovery data set showed an association between CNV losses within 16q12.2 and AD diagnosis (<italic>p </italic>=<italic> </italic>4.53 × 10<sup>−3</sup>). An overlapping CNV region from the validation data set exhibited the same direction of effect with respect to AD (<italic>p </italic>=<italic> </italic>0.051). This CNV region affects the genes <italic>CES1p1</italic> and <italic>CES1, </italic> which are members of the carboxylesterase (CES) family. The enzyme encoded by <italic>CES1</italic> 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 (<italic>p </italic>=<italic> </italic>1.9 × 10<sup>−3</sup>) 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.</p> </sec> <sec id="acer12364-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Overall, our study provides evidence that the specific CNVs at 16q12.2 contribute to the development of alcoholism in AA and European American populations.</p> </sec> </abstract>