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

TY - JOUR

T1 - Increased alcohol consumption as a cause of alcoholism, without similar evidence for depression

T2 - a Mendelian randomization study

AU - Wium-Andersen, Marie Kim

AU - Orsted, David Dynnes

AU - Tolstrup, Janne Schurmann

AU - Nordestgaard, Børge Grønne

N1 - © The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

PY - 2015/5/27

Y1 - 2015/5/27

N2 - 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.

AB - 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.

U2 - 10.1093/ije/dyu220

DO - 10.1093/ije/dyu220

M3 - Journal article

C2 - 25433705

SN - 0300-5771

VL - 526-539

SP - 526

EP - 539

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

IS - 14

ER -