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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 JenChyong,
Xuei Xiaoling,
Edenberg Howard J.,
Porjesz Bernice,
Bucholz Kathleen,
Goate Alison M.,
Foroud Tatiana
Publication year - 2015
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12153
Subject(s) - single nucleotide polymorphism , alcohol dependence , genome wide association study , genetics , substance dependence , heritability , snp , genetic association , addiction , biology , psychology , gene , psychiatry , genotype , alcohol , biochemistry
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 E uropean‐ A merican families in the C ollaborative S tudy on the G enetics of A lcoholism 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 [ S tudy of A ddiction: G enetics and E nvironment ( SAGE ); P = 0.02]. One SNP , rs2567261 in ARHGAP28 ( Rho GTP ase‐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.