A genome-wide association study of alcohol-dependence symptom counts in extended pedigrees identifies C15orf53.
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Hinrichs, A L
Le, N X H
Budde, J P
Koller, D L
Brooks, A I
Johnson, E O
Madden, P A F
Martin, N G
McClintick, J N
Montgomery, G W
Nurnberger, J I
Tischfield, J A
Whitfield, J B
Heath, A C
Edenberg, H J
Bierut, L J
Goate, A M
Journal titleMolecular psychiatry
Publication Begin page1218
Publication End page24
MetadataShow full item record
AbstractSeveral studies have identified genes associated with alcohol-use disorders (AUDs), but the variation in each of these genes explains only a small portion of the genetic vulnerability. The goal of the present study was to perform a genome-wide association study (GWAS) in extended families from the Collaborative Study on the Genetics of Alcoholism to identify novel genes affecting risk for alcohol dependence (AD). To maximize the power of the extended family design, we used a quantitative endophenotype, measured in all individuals: number of alcohol-dependence symptoms endorsed (symptom count (SC)). Secondary analyses were performed to determine if the single nucleotide polymorphisms (SNPs) associated with SC were also associated with the dichotomous phenotype, DSM-IV AD. This family-based GWAS identified SNPs in C15orf53 that are strongly associated with DSM-IV alcohol-dependence symptom counts (P=4.5 × 10(-8), inflation-corrected P=9.4 × 10(-7)). Results with DSM-IV AD in the regions of interest support our findings with SC, although the associations were less significant. Attempted replications of the most promising association results were conducted in two independent samples: nonoverlapping subjects from the Study of Addiction: Genes and Environment (SAGE) and the Australian Twin Family Study of AUDs (OZALC). Nominal association of C15orf53 with SC was observed in SAGE. The variant that showed strongest association with SC, rs12912251 and its highly correlated variants (D'=1, r(2) 0.95), have previously been associated with risk for bipolar disorder.
CitationWang JC, Foroud T, Hinrichs AL, Le NX, Bertelsen S, Budde JP, Harari O, Koller DL, Wetherill L, Agrawal A, Almasy L, Brooks AI, Bucholz K, Dick D, Hesselbrock V, Johnson EO, Kang S, Kapoor M, Kramer J, Kuperman S, Madden PA, Manz N, Martin NG, McClintick JN, Montgomery GW, Nurnberger JI Jr, Rangaswamy M, Rice J, Schuckit M, Tischfield JA, Whitfield JB, Xuei X, Porjesz B, Heath AC, Edenberg HJ, Bierut LJ, Goate AM. A genome-wide association study of alcohol-dependence symptom counts in extended pedigrees identifies C15orf53. Mol Psychiatry. 2013 Nov;18(11):1218-24. doi: 10.1038/mp.2012.143. Epub 2012 Oct 23. PMID: 23089632; PMCID: PMC3752321.
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