ALDH2 is associated to alcohol dependence and is the major genetic determinant of "daily maximum drinks" in a GWAS study of an isolated rural chinese sample

Ellen E. Quillen, Xiang Ding Chen, Laura Almasy, Fang Yang, Hao He, Xi Li, Xu Yi Wang, Tie Qiao Liu, Wei Hao, Hong Wen Deng, Henry R. Kranzler, Joel Gelernter

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Alcohol dependence (AD) is a moderately heritable phenotype with a small number of known risk genes mapped via linkage or candidate gene studies. We considered 313 males from among 595 members of documented, extended pedigrees in which AD segregates collected in Northern Hunan Province, China. A joint analysis of both males and females could not be performed as the difference in alcohol consumption variance was too large. Genome-wide association analyses were performed for approximately 300,000 single nucleotide polymorphisms (SNPs). Significant associations found in the ALDH2 region for AD (minimum P=4.73×10-8) and two AD-related phenotypes: flushing response (minimum P=4.75×10-26) and maximum drinks in a 24-hr period (minimum P=1.54×10-16). Association of previous candidate SNP, rs10774610 in CCDC63, was confirmed but resulted from linkage disequilibrium with ALDH2. ALDH2 is strongly associated with flushing response, AD, and maximum drinks in males, with nonsynonymous SNP rs671 explaining 29.2%, 7.9%, and 22.9% of phenotypic variation, respectively, in this sample. When rs671 was considered as a candidate SNP in females, it explained 23.6% of the variation in flushing response, but alcohol consumption rates were too low among females-despite familial enrichment for AD-for an adequate test of association for either AD or maximum drinks. These results support a mediating effect of aldehyde dehydrogenase deficiency on alcohol consumption in males and a secondary, culturally mediated limitation on alcohol consumption by females that should be appropriately modeled in future studies of alcohol consumption in populations where this may be a factor.

Original languageEnglish (US)
Pages (from-to)103-110
Number of pages8
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume165
Issue number2
DOIs
StatePublished - Mar 2014
Externally publishedYes

Fingerprint

Genome-Wide Association Study
Alcoholism
Alcohol Drinking
Single Nucleotide Polymorphism
Phenotype
Aldehyde Dehydrogenase
Linkage Disequilibrium
Pedigree
Genes
China
Population

Keywords

  • Alcohol dependence
  • Aldehyde dehydrogenase
  • Flushing response
  • Genome-wide association
  • Maximum drinks

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

ALDH2 is associated to alcohol dependence and is the major genetic determinant of "daily maximum drinks" in a GWAS study of an isolated rural chinese sample. / Quillen, Ellen E.; Chen, Xiang Ding; Almasy, Laura; Yang, Fang; He, Hao; Li, Xi; Wang, Xu Yi; Liu, Tie Qiao; Hao, Wei; Deng, Hong Wen; Kranzler, Henry R.; Gelernter, Joel.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 165, No. 2, 03.2014, p. 103-110.

Research output: Contribution to journalArticle

Quillen, Ellen E. ; Chen, Xiang Ding ; Almasy, Laura ; Yang, Fang ; He, Hao ; Li, Xi ; Wang, Xu Yi ; Liu, Tie Qiao ; Hao, Wei ; Deng, Hong Wen ; Kranzler, Henry R. ; Gelernter, Joel. / ALDH2 is associated to alcohol dependence and is the major genetic determinant of "daily maximum drinks" in a GWAS study of an isolated rural chinese sample. In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 2014 ; Vol. 165, No. 2. pp. 103-110.
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abstract = "Alcohol dependence (AD) is a moderately heritable phenotype with a small number of known risk genes mapped via linkage or candidate gene studies. We considered 313 males from among 595 members of documented, extended pedigrees in which AD segregates collected in Northern Hunan Province, China. A joint analysis of both males and females could not be performed as the difference in alcohol consumption variance was too large. Genome-wide association analyses were performed for approximately 300,000 single nucleotide polymorphisms (SNPs). Significant associations found in the ALDH2 region for AD (minimum P=4.73×10-8) and two AD-related phenotypes: flushing response (minimum P=4.75×10-26) and maximum drinks in a 24-hr period (minimum P=1.54×10-16). Association of previous candidate SNP, rs10774610 in CCDC63, was confirmed but resulted from linkage disequilibrium with ALDH2. ALDH2 is strongly associated with flushing response, AD, and maximum drinks in males, with nonsynonymous SNP rs671 explaining 29.2{\%}, 7.9{\%}, and 22.9{\%} of phenotypic variation, respectively, in this sample. When rs671 was considered as a candidate SNP in females, it explained 23.6{\%} of the variation in flushing response, but alcohol consumption rates were too low among females-despite familial enrichment for AD-for an adequate test of association for either AD or maximum drinks. These results support a mediating effect of aldehyde dehydrogenase deficiency on alcohol consumption in males and a secondary, culturally mediated limitation on alcohol consumption by females that should be appropriately modeled in future studies of alcohol consumption in populations where this may be a factor.",
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T1 - ALDH2 is associated to alcohol dependence and is the major genetic determinant of "daily maximum drinks" in a GWAS study of an isolated rural chinese sample

AU - Quillen, Ellen E.

AU - Chen, Xiang Ding

AU - Almasy, Laura

AU - Yang, Fang

AU - He, Hao

AU - Li, Xi

AU - Wang, Xu Yi

AU - Liu, Tie Qiao

AU - Hao, Wei

AU - Deng, Hong Wen

AU - Kranzler, Henry R.

AU - Gelernter, Joel

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