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Association of substance dependence phenotypes in the COGA sample.

  • Author(s): 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
  • et al.

Published Web Location

https://doi.org/10.1111/adb.12153
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.

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