Marie Kim Wium-Andersen1, David Dynnes Ørsted1, Janne Schurmann Tolstrup2, Børge Grønne Nordestgaard3. 1. Department of Clinical Biochemistry, and Copenhagen General Population Study, Copenhagen University Hospital, Herlev, Denmark, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark and Copenhagen City Heart Study, Copenhagen University Hospital, Frederiksberg, Denmark Department of Clinical Biochemistry, and Copenhagen General Population Study, Copenhagen University Hospital, Herlev, Denmark, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark and Copenhagen City Heart Study, Copenhagen University Hospital, Frederiksberg, Denmark Department of Clinical Biochemistry, and Copenhagen General Population Study, Copenhagen University Hospital, Herlev, Denmark, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark and Copenhagen City Heart Study, Copenhagen University Hospital, Frederiksberg, Denmark. 2. Department of Clinical Biochemistry, and Copenhagen General Population Study, Copenhagen University Hospital, Herlev, Denmark, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark and Copenhagen City Heart Study, Copenhagen University Hospital, Frederiksberg, Denmark. 3. Department of Clinical Biochemistry, and Copenhagen General Population Study, Copenhagen University Hospital, Herlev, Denmark, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark and Copenhagen City Heart Study, Copenhagen University Hospital, Frederiksberg, Denmark Department of Clinical Biochemistry, and Copenhagen General Population Study, Copenhagen University Hospital, Herlev, Denmark, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark and Copenhagen City Heart Study, Copenhagen University Hospital, Frederiksberg, Denmark Department of Clinical Biochemistry, and Copenhagen General Population Study, Copenhagen University Hospital, Herlev, Denmark, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark and Copenhagen City Heart Study, Copenhagen University Hospital, Frederiksberg, Denmark Department of Clinical Biochemistry, and Copenhagen General Population Study, Copenhagen University Hospital, Herlev, Denmark, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark and Copenhagen City Heart Study, Copenhagen University Hospital, Frederiksberg, Denmark Boerge.Nordestgaard@regionh.dk.
Abstract
BACKGROUND: Increased alcohol consumption has been associated with depression and alcoholism, but whether these associations are causal remains unclear. We tested whether alcohol consumption is causally associated with depression and alcoholism. METHODS: We included 78,154 men and women aged 20-100 years randomly selected in 1991-2010 from the general population of Copenhagen, Denmark, and genotyped 68,486 participants for two genetic variants in two alcohol dehydrogenase (ADH) genes, ADH-1B (rs1229984) and ADH-1C (rs698). We performed observational and causal analyses using a Mendelian randomization design with antidepressant medication use and hospitalization/death, with depression and alcoholism as outcomes. RESULTS: In prospective analyses, the multifactorially adjusted hazard ratio for participants reporting >6 drinks/day vs participants reporting 0.1-1 drinks/day was 1.28 (95% confidence interval, 1.00-1.65) for prescription antidepressant use, with a corresponding hazard ratio of 0.80 (0.45-1.45) for hospitalization/death with depression and of 11.7 (8.77-15.6) for hospitalization/death with alcoholism. For hospitalization/death with alcoholism, instrumental variable analysis yielded a causal odds ratio of 28.6 (95 % confidence interval 6.47-126) for an increase of 1 drink/day estimated from the combined genotype combination, whereas the corresponding multifactorially adjusted observational odds ratio was 1.28 (1.25-1.31). Corresponding odds ratios were 1.11 (0.67-1.83) causal and 1.04 (1.03-1.06) observational for prescription antidepressant use, and 4.52 (0.99-20.5) causal and 0.98 (0.94-1.03) observational for hospitalization/death with depression. CONCLUSIONS: These data indicate that the association between increased alcohol consumption and alcoholism is causal, without similar strong evidence for depression.
BACKGROUND: Increased alcohol consumption has been associated with depression and alcoholism, but whether these associations are causal remains unclear. We tested whether alcohol consumption is causally associated with depression and alcoholism. METHODS: We included 78,154 men and women aged 20-100 years randomly selected in 1991-2010 from the general population of Copenhagen, Denmark, and genotyped 68,486 participants for two genetic variants in two alcohol dehydrogenase (ADH) genes, ADH-1B (rs1229984) and ADH-1C (rs698). We performed observational and causal analyses using a Mendelian randomization design with antidepressant medication use and hospitalization/death, with depression and alcoholism as outcomes. RESULTS: In prospective analyses, the multifactorially adjusted hazard ratio for participants reporting >6 drinks/day vs participants reporting 0.1-1 drinks/day was 1.28 (95% confidence interval, 1.00-1.65) for prescription antidepressant use, with a corresponding hazard ratio of 0.80 (0.45-1.45) for hospitalization/death with depression and of 11.7 (8.77-15.6) for hospitalization/death with alcoholism. For hospitalization/death with alcoholism, instrumental variable analysis yielded a causal odds ratio of 28.6 (95 % confidence interval 6.47-126) for an increase of 1 drink/day estimated from the combined genotype combination, whereas the corresponding multifactorially adjusted observational odds ratio was 1.28 (1.25-1.31). Corresponding odds ratios were 1.11 (0.67-1.83) causal and 1.04 (1.03-1.06) observational for prescription antidepressant use, and 4.52 (0.99-20.5) causal and 0.98 (0.94-1.03) observational for hospitalization/death with depression. CONCLUSIONS: These data indicate that the association between increased alcohol consumption and alcoholism is causal, without similar strong evidence for depression.
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