Genome-wide association studies of alcohol dependence, DSM-IV criterion count and individual criteria.
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Carey, Caitlin E
Meyers, Jacquelyn L
Anokhin, Andrey P
Bennett, David A
Bucholz, Kathleen K
Chang, Katharine K
De Jager, Philip L
Dick, Danielle M
Nurnberger, John I
Scott, Denise M
Taylor, Robert E
Hariri, Ahmad R
Edenberg, Howard J
Goate, Alison M
KeywordDSM-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
polygenic risk score
Journal titleGenes, brain, and behavior
Publication Begin pagee12579
MetadataShow full item record
AbstractGenome-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 < .01; 0.61%-1.82% of variance). Identified novel variants (ie, rs1912461, rs61826952) were associated with differential central evoked theta power (loss - gain; P = .0037) and reward-related ventral striatum reactivity (P = .008), respectively. This study suggests that studying individual criteria may unveil new insights into the genetic etiology of AD liability.
CitationLai D, Wetherill L, Bertelsen S, Carey CE, Kamarajan C, Kapoor M, Meyers JL, Anokhin AP, Bennett DA, Bucholz KK, Chang KK, De Jager PL, Dick DM, Hesselbrock V, Kramer J, Kuperman S, Nurnberger JI Jr, Raj T, Schuckit M, Scott DM, Taylor RE, Tischfield J, Hariri AR, Edenberg HJ, Agrawal A, Bogdan R, Porjesz B, Goate AM, Foroud T. Genome-wide association studies of alcohol dependence, DSM-IV criterion count and individual criteria. Genes Brain Behav. 2019 Jul;18(6):e12579. doi: 10.1111/gbb.12579. Epub 2019 Jun 4. PMID: 31090166; PMCID: PMC6612573.
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Except where otherwise noted, this item's license is described as © 2019 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.
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