Association of substance dependence phenotypes in the COGA sample.
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.
Indiana University School of Medicine, Indianapolis, IN, USA.
Leah
L
Wetherill
Arpana
A
Agrawal
Manav
M
Kapoor
Sarah
S
Bertelsen
Laura J
LJ
Bierut
Andrew
A
Brooks
Danielle
D
Dick
Michie
M
Hesselbrock
Victor
V
Hesselbrock
Daniel L
DL
Koller
Nhung
N
Le
John I
JI
Nurnberger
Jessica E
JE
Salvatore
Marc
M
Schuckit
Jay A
JA
Tischfield
Jen-Chyong
JC
Wang
Xiaoling
X
Xuei
Howard J
HJ
Edenberg
Bernice
B
Porjesz
Kathleen
K
Bucholz
Alison M
AM
Goate
Tatiana
T
Foroud
D000293:Adolescent; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D019966:Substance-Related Disorders / Q000235:genetics*; D055815:Young Adult
C000603954:ARHGAP28 protein, human; D020690:GTPase-Activating Proteins; C085379:rho GTPase-activating protein
Alcohol dependence; cannabis dependence; cocaine dependence; common genetic liability; drug dependence; opioid dependence