Increased alcohol consumption as a cause of alcoholism, without similar evidence for depression: a Mendelian randomization study.
Increased alcohol consumption as a cause of alcoholism, without similar evidence for depression: a Mendelian randomization study.
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DOI：
10.1093/ije/dyu220
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发表时间：
2015-04
影响因子：
7.7
通讯作者：
M. K. Wium-Andersen;D. D. Ørsted-D.;J. Tolstrup;B. Nordestgaard
中科院分区：
文献类型：
--
作者：
M. K. Wium-Andersen;D. D. Ørsted-D.;J. Tolstrup;B. Nordestgaard
饮酒量的增加与抑郁症和酒精中毒有关，但这些联系是否是因果关系仍不清楚。我们测试了饮酒是否与抑郁症和酗酒有因果关系。我们纳入了1991-2010年从丹麦哥本哈根的一般人群中随机选择的78，154名年龄在20-100岁之间的男性和女性，并对68，486名参与者进行了两种乙醇脱氢酶（ADH）基因（ADH-1B（rs 1229984）和ADH-1C（rs698））的两种遗传变异的基因分型。我们采用孟德尔随机设计进行了观察和因果分析，抗抑郁药物的使用和住院/死亡，抑郁和酗酒作为结局。结果在前瞻性分析中，多因素调整的风险比为参与者报告>6杯/天与参与者报告0.1-1杯/天为1.28（95%置信区间，1.00-1.65）对于处方抗抑郁药的使用，抑郁症住院/死亡的相应风险比为0.80（0.45-1.45），酗酒住院/死亡的相应风险比为11.7（8.77-15.6）。对于因酒精中毒而住院/死亡，工具变量分析得出的因果比值比为28.6（95%置信区间6.47-126），从联合基因型组合中估计每天增加1杯酒，而相应的多因素调整观察比值比为1.28（1.25-1.31）。处方抗抑郁药使用的相应比值比为1.11（0.67-1.83）因果关系和1.04（1.03-1.06）观察性，抑郁症住院/死亡的相应比值比为4.52（0.99-20.5）因果关系和0.98（0.94-1.03）观察性。结论：这些数据表明，增加饮酒量和酗酒之间的关联是因果关系，没有类似的强有力的证据抑郁症。
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.