Mendelian randomization · 2016

Increased alcohol consumption as a cause of alcoholism, without similar evidence for depression: a Mendelian randomization study.

MK Wium-Andersen, DD Ørsted, JS Tolstrup, BG Nordestgaard. International journal of epidemiology.

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.

Open source doi:10.1093/ije/dyu220 PMID 25433705

Edges that cite this paper

Three Mendelian randomization files of alcohol on depression disagree: two ADH variants in 68,486 Copenhagen adults are null for antidepressant use, UK Biobank beer and spirits instruments raise major depression until insomnia and smoking enter the model, and ALDH2 plus ADH1B in 476 Chinese adults point the other way.

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