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Am J Med Genet B Neuropsychiatr Genet. 2015 Jul;168B(5):347-53. doi: 10.1002/ajmg.b.32316. Epub 2015 Apr 29.

Eye color: A potential indicator of alcohol dependence risk in European Americans.

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Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont.
Cell, Molecular, and Biomedical Sciences Graduate Program, University of Vermont, Burlington, Vermont.
Departmentof Psychiatry, University of Pennsylvania School of Medicine and VAMC 4 MIRECC, Philadelphia VAMC, Philadelphia, Pennsylvania.
Departments of Medicine (Biomedical Genetics), Neurology, Ophthalmology, Genetics & Genomics, Biostatistics, and Epidemiology, Boston University Schools of Medicine and Public Health, Boston, Massachusetts.
Department of Psychiatry, School of Medicine, Yale University, New Haven, Connecticut.
Department of Genetics, School of Medicine, Yale University, New Haven, Connecticut.
Connecticutand Department of Neurobiology, Yale University School of Medicine, VA Connecticut Healthcare Center, West Haven, New Haven, Connecticut.
Department of Computer Science, University of Vermont, Burlington, Vermont.
Neuroscience, Behavior, and Health Initiative, University of Vermont, Burlington, Vermont.


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.


alcohol dependence; association; drinking; ethanol; eye pigmentation; melanogenesis

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