BACKGROUND: Genome-wide association (GWA) studies regarding the quantitative trait of alcohol consumption are limited. OBJECTIVE: The objective of the study was to explore genetic loci associated with the amount of alcohol consumed. DESIGN: We conducted a GWA study with discovery data on single nucleotide polymorphisms (SNPs) for 1721 Korean male drinkers aged 40-69 y who were included in an urban population-based cohort. Another sample that comprised 1113 male drinkers who were from an independent cohort enrolled in a rural area served as a resource for replication. At baseline (18 June 2001 through 29 January 2003), members of both cohorts provided information on average daily alcohol consumptions, and their DNA samples were collected for genotyping. RESULTS: We tested 315,914 SNPs of discovery data by using multivariate linear regression analysis adjusted for age and smoking, and 12 SNPs on chromosome 12q24 had genome-wide significant associations with alcohol consumption; adjusted P values by using Bonferroni correction were 1.6 × 10(-5) through 5.8 × 10(-46). We observed most SNPs in intronic regions and showed that the genes that harbor SNPs were C12orf51, CCDC63, MYL2, OAS3, CUX2, and RPH3A. In particular, signals in or near C12orf51, CCDC63, and MYL2 were successfully replicated in the test for 317,951 SNPs; rs2074356 in C12orf51 was in high linkage disequilibrium with SNPs in ALDH2, but other SNPs were not. CONCLUSIONS: In a GWA study, we identified loci and alleles highly associated with alcohol consumption. The findings suggest the need for further investigations on the genetic propensity for drinking excessive amounts of alcohol.
BACKGROUND: Genome-wide association (GWA) studies regarding the quantitative trait of alcohol consumption are limited. OBJECTIVE: The objective of the study was to explore genetic loci associated with the amount of alcohol consumed. DESIGN: We conducted a GWA study with discovery data on single nucleotide polymorphisms (SNPs) for 1721 Korean male drinkers aged 40-69 y who were included in an urban population-based cohort. Another sample that comprised 1113 male drinkers who were from an independent cohort enrolled in a rural area served as a resource for replication. At baseline (18 June 2001 through 29 January 2003), members of both cohorts provided information on average daily alcohol consumptions, and their DNA samples were collected for genotyping. RESULTS: We tested 315,914 SNPs of discovery data by using multivariate linear regression analysis adjusted for age and smoking, and 12 SNPs on chromosome 12q24 had genome-wide significant associations with alcohol consumption; adjusted P values by using Bonferroni correction were 1.6 × 10(-5) through 5.8 × 10(-46). We observed most SNPs in intronic regions and showed that the genes that harbor SNPs were C12orf51, CCDC63, MYL2, OAS3, CUX2, and RPH3A. In particular, signals in or near C12orf51, CCDC63, and MYL2 were successfully replicated in the test for 317,951 SNPs; rs2074356 in C12orf51 was in high linkage disequilibrium with SNPs in ALDH2, but other SNPs were not. CONCLUSIONS: In a GWA study, we identified loci and alleles highly associated with alcohol consumption. The findings suggest the need for further investigations on the genetic propensity for drinking excessive amounts of alcohol.
Authors: Arpana Agrawal; Neal D Freedman; Yu-Ching Cheng; Peng Lin; John R Shaffer; Qi Sun; Kira Taylor; Brian Yaspan; John W Cole; Marilyn C Cornelis; Rebecca S DeSensi; Annette Fitzpatrick; Gerardo Heiss; Jae H Kang; Jeffrey O'Connell; Siiri Bennett; Ebony Bookman; Kathleen K Bucholz; Neil Caporaso; Richard Crout; Danielle M Dick; Howard J Edenberg; Alison Goate; Victor Hesselbrock; Steven Kittner; John Kramer; John I Nurnberger; Lu Qi; John P Rice; Marc Schuckit; Rob M van Dam; Eric Boerwinkle; Frank Hu; Steven Levy; Mary Marazita; Braxton D Mitchell; Louis R Pasquale; Laura J Bierut Journal: Am J Clin Nutr Date: 2012-02-01 Impact factor: 7.045
Authors: Jacqueline M Otto; Christian S Hendershot; Susan E Collins; Tiebing Liang; Tamara L Wall Journal: Alcohol Clin Exp Res Date: 2012-05-16 Impact factor: 3.455