Conflict of interest: Henry Kranzler has been a consultant or advisory board member for the following pharmaceutical companies: Alkermes, Lilly, Lundbeck, Otsuka, Pfizer, and Roche. He is also a member of the American Society of Clinical Psychopharmacology's Alcohol Clinical Trials Initiative, which is supported by Alkermes, Ethypharm, Lilly, Lundbeck, AbbVie, and Pfizer. All the other authors declare no potential conflict of interest.
Eye color: A potential indicator of alcohol dependence risk in European Americans
Version of Record online: 29 APR 2015
© 2015 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 168, Issue 5, pages 347–353, July 2015
How to Cite
2015. Eye Color: A Potential Indicator of Alcohol Dependence Risk in European Americans. Am J Med Genet Part B 168B:347–353., , , , .
- Issue online: 10 JUN 2015
- Version of Record online: 29 APR 2015
- Manuscript Accepted: 2 APR 2015
- Manuscript Received: 6 JAN 2015
- Start-up Fund of the University of Vermont
- alcohol dependence;
- eye pigmentation;
In archival samples of European-ancestry subjects, light-eyed individuals have been found to consume more alcohol than dark-eyed individuals. No published population-based studies have directly tested the association between alcohol dependence (AD) and eye color. We hypothesized that light-eyed individuals have a higher prevalence of AD than dark-eyed individuals. A mixture model was used to select a homogeneous sample of 1,263 European-Americans and control for population stratification. After quality control, we conducted an association study using logistic regression, adjusting for confounders (age, sex, and genetic ancestry). We found evidence of association between AD and blue eye color (P = 0.0005 and odds ratio = 1.83 (1.31–2.57)), supporting light eye color as a risk factor relative to brown eye color. Network-based analyses revealed a statistically significant (P = 0.02) number of genetic interactions between eye color genes and AD-associated genes. We found evidence of linkage disequilibrium between an AD-associated GABA receptor gene cluster, GABRB3/GABRG3, and eye color genes, OCA2/HERC2, as well as between AD-associated GRM5 and pigmentation-associated TYR. Our population-phenotype, network, and linkage disequilibrium analyses support association between blue eye color and AD. Although we controlled for stratification we cannot exclude underlying occult stratification as a contributor to this observation. Although replication is needed, our findings suggest that eye pigmentation information may be useful in research on AD. Further characterization of this association may unravel new AD etiological factors. © 2015 Wiley Periodicals, Inc.