학술논문
Substance dependence
Document Type
article
Author
Wetherill, Leah; Agrawal, Arpana; Kapoor, Manav; Bertelsen, Sarah; Bierut, Laura J; Brooks, Andrew; Dick, Danielle; Hesselbrock, Michie; Hesselbrock, Victor; Koller, Daniel L; Le, Nhung; Nurnberger, John I; Salvatore, Jessica E; Schuckit, Marc; Tischfield, Jay A; Wang, Jen‐Chyong; Xuei, Xiaoling; Edenberg, Howard J; Porjesz, Bernice; Bucholz, Kathleen; Goate, Alison M; Foroud, Tatiana
Source
Addiction Biology. 20(3)
Subject
Language
Abstract
Alcohol and drug use disorders are individually heritable (50%). Twin studies indicate that alcohol and substance use disorders share common genetic influences, and therefore may represent a more heritable form of addiction and thus be more powerful for genetic studies. This study utilized data from 2322 subjects from 118 European-American families in the Collaborative Study on the Genetics of Alcoholism sample to conduct genome-wide association analysis of a binary and a continuous index of general substance dependence liability. The binary phenotype (ANYDEP) was based on meeting lifetime criteria for any DSM-IV dependence on alcohol, cannabis, cocaine or opioids. The quantitative trait (QUANTDEP) was constructed from factor analysis based on endorsement across the seven DSM-IV criteria for each of the four substances. Heritability was estimated to be 54% for ANYDEP and 86% for QUANTDEP. One single-nucleotide polymorphism (SNP), rs2952621 in the uncharacterized gene LOC151121 on chromosome 2, was associated with ANYDEP (P = 1.8 × 10(-8) ), with support from surrounding imputed SNPs and replication in an independent sample [Study of Addiction: Genetics and Environment (SAGE); P = 0.02]. One SNP, rs2567261 in ARHGAP28 (Rho GTPase-activating protein 28), was associated with QUANTDEP (P = 3.8 × 10(-8) ), and supported by imputed SNPs in the region, but did not replicate in an independent sample (SAGE; P = 0.29). The results of this study provide evidence that there are common variants that contribute to the risk for a general liability to substance dependence.