1. Genome‐wide association studies of alcohol dependence, DSM‐IV criterion count and individual criteria
- Author
-
Lai, Dongbing, Wetherill, Leah, Bertelsen, Sarah, Carey, Caitlin E, Kamarajan, Chella, Kapoor, Manav, Meyers, Jacquelyn L, Anokhin, Andrey P, Bennett, David A, Bucholz, Kathleen K, Chang, Katharine K, De Jager, Philip L, Dick, Danielle M, Hesselbrock, Victor, Kramer, John, Kuperman, Samuel, Nurnberger, John I, Raj, Towfique, Schuckit, Marc, Scott, Denise M, Taylor, Robert E, Tischfield, Jay, Hariri, Ahmad R, Edenberg, Howard J, Agrawal, Arpana, Bogdan, Ryan, Porjesz, Bernice, Goate, Alison M, and Foroud, Tatiana
- Subjects
Biological Sciences ,Genetics ,Human Genome ,Brain Disorders ,Alcoholism ,Alcohol Use and Health ,Substance Misuse ,Neurosciences ,Good Health and Well Being ,Adolescent ,Adult ,Black or African American ,Alcohol Dehydrogenase ,Alcoholism ,Diagnostic and Statistical Manual of Mental Disorders ,Female ,Humans ,Male ,Polymorphism ,Single Nucleotide ,Reward ,Theta Rhythm ,Ventral Striatum ,White People ,alcohol dependence ,DSM-IV alcohol dependence criterion ,DSM-IV criterion count ,DSM-IV individual criteria ,event-related theta oscillations ,functional magnetic resonance imaging ,genome-wide association study ,item response analysis ,meta-analysis ,polygenic risk score ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Neurology & Neurosurgery - Abstract
Genome-wide association studies (GWAS) of alcohol dependence (AD) have reliably identified variation within alcohol metabolizing genes (eg, ADH1B) but have inconsistently located other signals, which may be partially attributable to symptom heterogeneity underlying the disorder. We conducted GWAS of DSM-IV AD (primary analysis), DSM-IV AD criterion count (secondary analysis), and individual dependence criteria (tertiary analysis) among 7418 (1121 families) European American (EA) individuals from the Collaborative Study on the Genetics of Alcoholism (COGA). Trans-ancestral meta-analyses combined these results with data from 3175 (585 families) African-American (AA) individuals from COGA. In the EA GWAS, three loci were genome-wide significant: rs1229984 in ADH1B for AD criterion count (P = 4.16E-11) and Desire to cut drinking (P = 1.21E-11); rs188227250 (chromosome 8, Drinking more than intended, P = 6.72E-09); rs1912461 (chromosome 15, Time spent drinking, P = 1.77E-08). In the trans-ancestral meta-analysis, rs1229984 was associated with multiple phenotypes and two additional loci were genome-wide significant: rs61826952 (chromosome 1, DSM-IV AD, P = 8.42E-11); rs7597960 (chromosome 2, Time spent drinking, P = 1.22E-08). Associations with rs1229984 and rs18822750 were replicated in independent datasets. Polygenic risk scores derived from the EA GWAS of AD predicted AD in two EA datasets (P
- Published
- 2019