title: Excessive alcohol consumption increases mortality in later life: a genetic analysis of the health in men cohort study.
abstract: We designed this cohort study of men aged 70-89 years to determine if excessive alcohol use increases mortality. They reported history of alcohol use (never, past, ≤ two daily drinks, two to four daily drinks, four to six daily drinks, > six daily drinks) and donated a blood sample in 2001-2004. We determined the ADH1B rs1229984 G>A polymorphism and retrieved mortality data from the Western Australian Data Linkage System. Other study measures included age, education, body mass index, smoking, and history of hypertension, diabetes, chronic respiratory diseases, coronary heart disease and stroke. Of the 3496 participants, 225 (6.4 percent) carried the ADH1B rs1229984 G>A polymorphism. Carriers consumed significantly less alcohol than non-carriers. The adjusted mortality hazard ratio (MHR, 95 percent confidence interval-95%CI) over 8.0 years (range: 10 weeks to 11.2 years) relative to never drinkers was 1.15 (95%CI = 0.86, 1.55) for past drinkers, 0.98 (95%CI = 0.76, 1.25) for men consuming ≤ two daily drinks, 1.13 (95%CI = 0.85, 1.49) for two to four drinks, 1.18 (95%CI = 0.81, 1.71) for four to six drinks and 1.87 (95%CI = 1.11, 3.12) for those consuming more than six daily drinks on a regular basis. The MHR associated with the ADH1B rs1229984 G>A polymorphism was 0.68 (95%CI = 0.54, 0.87). Excessive alcohol use in later life is associated with increased mortality, and this association is likely to be causal. We found no evidence that light to moderate alcohol use decreases the mortality of older men. Health messages regarding the safe use of alcohol in older age may benefit from taking these findings into account.
authors.affiliation: School of Psychiatry and Clinical Neurosciences, University of Western Australia, Australia.|WA Centre for Health and Ageing, Centre for Medical Research, Australia.|Department of Psychiatry, Royal Perth Hospital, Australia.
authors.forename: Osvaldo P
authors.initials: OP
authors.lastname: Almeida
authors.affiliation: WA Centre for Health and Ageing, Centre for Medical Research, Australia.
authors.forename: Kieran
authors.initials: K
authors.lastname: McCaul
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Australia.|Department of Neurology, Sir Charles Gairdner Hospital, Australia.
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Australia.|Department of Endocrinology, Fremantle and Fiona Stanley Hospitals, Australia.
authors.forename: Bu B
authors.initials: BB
authors.lastname: Yeap
authors.affiliation: Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Australia.|Department of Vascular and Endovascular Surgery, The Townsville Hospital, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Golledge
authors.affiliation: WA Centre for Health and Ageing, Centre for Medical Research, Australia.|School of Medicine and Pharmacology, University of Western Australia, Australia.|Department of Geriatric Medicine, Royal Perth Hospital, Australia.
authors.forename: Leon
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; D000437:Alcoholism / Q000453:epidemiology* / Q000235:genetics; D002423:Cause of Death; D002908:Chronic Disease; D003327:Coronary Disease / Q000453:epidemiology; D003920:Diabetes Mellitus / Q000453:epidemiology; D006579:Heterozygote; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D008297:Male; D009026:Mortality; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012140:Respiratory Tract Diseases / Q000453:epidemiology; D012907:Smoking / Q000453:epidemiology; D020521:Stroke / Q000453:epidemiology; D014904:Western Australia / Q000453:epidemiology
chemical_list: C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase
keywords: Mendelian randomisation; ageing; alcohol; alcohol dehydrogenase; mortality; rs1229984 polymorphism