Ellen E. Quillen and Xiang-Ding Chen contributed equally to this work.
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
Article first published online: 26 NOV 2013
© 2013 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 165, Issue 2, pages 103–110, March 2014
How to Cite
2013. 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. Am J Med Genet Part B. 165B:103–110., , , , , , , , , , , .
Conflict of Interest: Dr. Kranzler has been a paid consultant or advisory board member for Alkermes, Lilly, Lundbeck, Pfizer, and Roche and has received honoraria from the Alcohol Clinical Trials Initiative (ACTIVE) of the American Society of Clinical Psychopharmacology, which is supported by Lilly, Lundbeck, Abbott, and Pfizer.
- Issue published online: 6 FEB 2014
- Article first published online: 26 NOV 2013
- Manuscript Accepted: 21 OCT 2013
- Manuscript Received: 2 AUG 2013
- NIAAA. Grant Numbers: R21 AA015973, P50 AA12870, K24 AA013736
- NIDA. Grant Number: R01 DA12849
- NIMH. Grant Number: MH059490
- SBC Foundation
- alcohol dependence;
- maximum drinks;
- flushing response;
- genome-wide association;
- aldehyde dehydrogenase
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. © 2013 Wiley Periodicals, Inc.