Wetherill, LeahAgrawal, ArpanaKapoor, ManavBertelsen, SarahBierut, Laura J.Brooks, AndrewDick, DanielleHesselbrock, MichieHesselbrock, VictorKoller, Daniel L.Le, NhungNurnberger Jr., John I.Salvatore, Jessica E.Schuckit, MarcTischfield, Jay A.Wang, Jen-ChyongXuei, XiaolingEdenberg, Howard J.Porjesz, BerniceBucholz, KathleenGoate, Alison M.Foroud, Tatiana2017-07-132017-07-132015-05Wetherill, L., Agrawal, A., Kapoor, M., Bertelsen, S., Bierut, L. J., Brooks, A., … Foroud, T. (2015). Association of substance dependence phenotypes in the COGA sample. Addiction Biology, 20(3), 617–627. http://doi.org/10.1111/adb.12153https://hdl.handle.net/1805/13434Alcohol 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.en-USPublisher PolicyAlcohol dependenceCannabis dependenceCocaine dependenceCommon genetic liabilityDrug dependenceOpioid dependenceArticle