title: Genome-wide association study of copy number variants suggests LTBP1 and FGD4 are important for alcohol drinking.
abstract: 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.
authors.affiliation: Center of System Biomedical Sciences, University of Shanghai for Science and Technology, Shanghai, People's Republic of China.
authors.forename: Yu-Fang
authors.initials: YF
authors.lastname: Pei
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Tie-Lin
authors.initials: TL
authors.lastname: Yang
authors.forename: Yingying
authors.initials: Y
authors.lastname: Han
authors.forename: Rong
authors.initials: R
authors.lastname: Hai
authors.forename: Shu
authors.initials: S
authors.lastname: Ran
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Xue-Zhen
authors.initials: XZ
authors.lastname: Zhu
authors.forename: Xingguang
authors.initials: X
authors.lastname: Luo
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D006801:Humans; D053779:Latent TGF-beta Binding Proteins / Q000235:genetics*; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: C485164:FGD4 protein, human; C509032:LTBP1 protein, human; D053779:Latent TGF-beta Binding Proteins; D008840:Microfilament Proteins