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Genomewide Association Study for Maximum Number of Alcoholic Drinks in European Americans and African Americans
Author(s) -
Xu Ke,
Kranzler Henry R.,
Sherva Richard,
Sartor Carolyn E.,
Almasy Laura,
Koesterer Ryan,
Zhao Hongyu,
Farrer Lindsay A.,
Gelernter Joel
Publication year - 2015
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12751
Subject(s) - genome wide association study , adh1b , single nucleotide polymorphism , snp , genetic association , genetics , chromosome , medicine , biology , genotype , gene , branched chain alpha keto acid dehydrogenase complex , biochemistry , dehydrogenase , enzyme
Background We conducted a genomewide association study ( GWAS ) for maximum number of alcoholic drinks consumed in a 24‐hour period (“MaxDrinks”), in 2 independent samples comprised of over 9,500 subjects, following up on our GWAS for alcohol dependence ( AD ) in European Americans ( EA s) and African Americans ( AA s). Methods The samples included our GWAS samples (Yale‐ UP enn) recruited for studies of the genetics of drug or AD, and a publicly available sample: the Study of Addiction: Genetics and Environment ( SAGE ). Genomewide association analysis was performed for ~890,000 single nucleotide polymorphisms ( SNP s) using linear association random effects models. EAs and AAs were separately analyzed. Results The results confirmed significant associations of the well‐known functional loci at ADH 1B with MaxDrinks in EA s (rs1229984 Arg48His p = 5.96 × 10 −15 ) and AA s (rs2066702 Arg370Cys , p = 2.50 × 10 −10 ). The region of significant association on chromosome 4 was extended to LOC 100507053 in AA s but not EA s. We also identified potentially novel significant common SNP s for MaxDrinks in EA s in the Yale‐ UP enn sample: rs1799876 at SERPINC 1 on chromosome 1 (4.00 × 10 −8 ) and rs2309169 close to ANKRD 36 on chromosome 2 ( p = 5.58 × 10 −9 ). After adjusting for the peak SNP rs1229984 on ADH 1B , rs1799876 was nearly significant ( p = 1.99 × 10 −7 ) and rs2309169 remained highly significant (2.12 × 10 −9 ). Conclusions The results provide further support that ADH 1B modulates alcohol consumption. Future replications of potential novel loci are warranted. This is the largest MaxDrinks GWAS to date, the first in AA s.