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.
Int J Epidemiol. 2015 Apr;44(2):526-39. doi: 10.1093/ije/dyu220. Epub 2014 Nov 29.
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.
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.
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.
These data indicate that the association between increased alcohol consumption and alcoholism is causal, without similar strong evidence for depression.
饮酒量增加与抑郁和酗酒有关，但这些关联是否具有因果关系尚不清楚。我们检验了饮酒是否与抑郁和酗酒具有因果关系。
我们纳入了丹麦哥本哈根的普通人群中，在 1991 年至 2010 年间随机选择的 78154 名 20-100 岁的男性和女性，并对 68486 名参与者的两种酒精脱氢酶（ADH）基因（ADH-1B[rs1229984]和 ADH-1C[rs698]）中的两个遗传变异进行了基因分型。我们使用基于孟德尔随机化设计的观察性和因果分析方法，以抗抑郁药物的使用和住院/死亡为结局，来评估抑郁和酗酒的情况。
在前瞻性分析中，与报告 0.1-1 杯/天相比，报告 >6 杯/天的参与者使用处方抗抑郁药的多因素调整危险比为 1.28（95%置信区间，1.00-1.65），与抑郁相关的住院/死亡率的危险比为 0.80（0.45-1.45），与酗酒相关的住院/死亡率的危险比为 11.7（8.77-15.6）。对于酗酒相关的住院/死亡率，通过对来自组合基因型的 1 杯/天的增量估计，工具变量分析得出的因果比值为 28.6（95%置信区间为 6.47-126），而多因素调整的观察比值为 1.28（1.25-1.31）。相应的因果比值为 1.11（0.67-1.83）和 1.04（1.03-1.06）用于处方抗抑郁药的使用，相应的观察比值为 4.52（0.99-20.5）和 0.98（0.94-1.03）用于与抑郁相关的住院/死亡率。
这些数据表明，饮酒量增加与酗酒之间的关联具有因果关系，但与抑郁之间没有类似的强有力证据。
