title: The triangular association of ADH1B genetic polymorphism, alcohol consumption and the risk of depression in older men.
abstract: Alcohol use, particularly alcohol abuse and dependence, are associated with increased risk of depression. Current diagnostic criteria suggest that the relationship is causal, but the evidence has only been derived from observational studies that are subject to confounding and bias. Given the logistic and ethical constraints that would be associated with a trial of alcohol use to prevent depression, we aimed to complete a Mendelian randomization study to determine if a genetic polymorphism associated with alcohol abuse and dependence (ADH1B rs1229984 G-->A) contributed to modulate the risk of depression in a community-derived cohort of older men. This retrospective analysis of a cohort of 3873 community-dwelling men aged 65-83 years living in the metropolitan region of Perth, Western Australia, investigated the triangular association between the rs1229984 G-->A polymorphism and alcohol use and, after 3.2-8.2 years, the presence of current depression or history of depression. The mean number of standard drinks consumed per week (n; standard deviation; range) according to genotype was AA 1.8 (17; 2.7; 0-7), GA 5.9 (262; 7.5; 0-35), GG 8.5 (3594; 10.9; 0-140) (GG>AA, GG>GA; P<0.001). Consumption of 1 or 2 drinks per day decreased the odds of depression (n=610) by 30 and 40%, whereas consumption of more than six drinks daily more than doubled the odds of depression (odds ratio: 2.12, 95% confidence interval: 1.02, 4.40). The ADH1B rs1229984 G-->A polymorphism was not associated with current or past depression (P=0.857). In addition, the presence of the A allele did not interact with the alcohol use to modulate the risk of depression (P=0.725). These results suggest that alcohol consumption does not cause or prevent depression in older men.
authors.affiliation: 1] School of Psychiatry & Clinical Neurosciences (M573), University of Western Australia, Perth, WA, Australia [2] WA Centre for Health & Ageing, Centre for Medical Research, Perth, WA, Australia [3] Department of Psychiatry, Royal Perth Hospital, Perth, WA, Australia.
authors.forename: O P
authors.initials: OP
authors.lastname: Almeida
authors.affiliation: 1] School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia [2] Department of Neurology, Royal Perth Hospital, Perth, WA, Australia.
authors.forename: G J
authors.initials: GJ
authors.lastname: Hankey
authors.affiliation: 1] School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia [2] Department of Endocrinology, Fremantle Hospital, Fremantle, WA, Australia.
authors.forename: B B
authors.initials: BB
authors.lastname: Yeap
authors.affiliation: Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, Townsville, QLD, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Golledge
authors.affiliation: 1] WA Centre for Health & Ageing, Centre for Medical Research, Perth, WA, Australia [2] School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia [3] Department of Geriatric Medicine, Royal Perth Hospital, Perth, WA, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Flicker
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000453:epidemiology / Q000235:genetics*; D003863:Depression / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012307:Risk Factors; D014904:Western Australia / Q000453:epidemiology
chemical_list: C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase
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