Genome-Wide Association Study of Copy Number Variants Suggests LTBP1 and FGD4 Are Important for Alcohol Drinking

• Published in: PloS one Vol. 7; no. 1; p. e30860
• Main Authors: Pei, Yu-Fang, Zhang, Lei, Yang, Tie-Lin, Han, Yingying, Hai, Rong, Ran, Shu, Tian, Qing, Shen, Hui, Li, Jian, Zhu, Xue-Zhen, Luo, Xingguang, Deng, Hong-Wen
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25.01.2012; Public Library of Science (PLoS)
• Subjects: Adult; Advertising executives; Alcohol; Alcohol Drinking - genetics; Alcohol use; Alcoholic beverages; Alcoholism; Alcohols; Asian Continental Ancestry Group - genetics; Biology; Cdc42 protein; Clustering; Copy number; Crohn's disease; Crohns disease; Dehydrogenases; Disease susceptibility; DNA Copy Number Variations - genetics; Drinking; Drinking (Alcoholic beverages); Drinking behavior; Drug dependence; European Continental Ancestry Group - genetics; Female; Gene expression; Genes; Genetic aspects; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genomics; Genotyping; Genotyping Techniques; Growth factors; Hormone replacement therapy; Humans; Laboratories; Latent TGF-beta Binding Proteins - genetics; Male; Medicine; Metabolism; Microfilament Proteins - genetics; Middle Aged; Physiological aspects; Polymorphism, Single Nucleotide - genetics; Protein transport; Psychopharmacology; Science; Studies; Transforming growth factor-b1; Trends; White people; γ-Aminobutyric acid A receptors; Louisiana; United States > US; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0030860

Alcohol dependence (AD) is a complex disorder characterized by psychiatric and physiological dependence on alcohol. AD is reflected by regular alcohol drinking, which is highly inheritable. In this study, to identify susceptibility genes associated with alcohol drinking, we performed a genome-wide association study of copy number variants (CNVs) in 2,286 Caucasian subjects with Affymetrix SNP6.0 genotyping array. We replicated our findings in 1,627 Chinese subjects with the same genotyping array. We identified two CNVs, CNV207 (combined p-value 1.91E-03) and CNV1836 (combined p-value 3.05E-03) that were associated with alcohol drinking. CNV207 and CNV1836 are located at the downstream of genes LTBP1 (870 kb) and FGD4 (400 kb), respectively. LTBP1, by interacting TGFB1, may down-regulate enzymes directly participating in alcohol metabolism. FGD4 plays a role in clustering and trafficking GABA(A) receptor and subsequently influence alcohol drinking through activating CDC42. Our results provide suggestive evidence that the newly identified CNV regions and relevant genes may contribute to the genetic mechanism of alcohol dependence.