Conventional and genetic evidence on alcohol and vascular disease aetiology: a prospective study of 500 000 men and women in China

作者：Iona Y. Millwood, Robin Walters, Xue W. Mei, Canqing Yu, Ling Yang, Zheng Bian, Derrick Bennett, Yiping Chen, Caixia Dong, Ruying Hu, Gang Zhou, Bo Yu, Weifang Jia, Sarah Parish, Robert Clarke, George Davey Smith, Rory Collins, Michael V. Holmes, Liming Li, Richard Peto, Zhengming Chen · 发表于：The Lancet · 年份：2019 · DOI：10.1016/s0140-6736(18)31772-0 · 被引用次数：527 · 研究领域：Alcohol Consumption and Health Effects、Substance Abuse Treatment and Outcomes、Alcoholism and Thiamine Deficiency

BACKGROUND: Moderate alcohol intake has been associated with reduced cardiovascular risk in many studies, in comparison with abstinence or with heavier drinking. Studies in east Asia can help determine whether these associations are causal, since two common genetic variants greatly affect alcohol drinking patterns. We used these two variants to assess the relationships between cardiovascular risk and genotype-predicted mean alcohol intake in men, contrasting the findings in men with those in women (few of whom drink). METHODS: The prospective China Kadoorie Biobank enrolled 512 715 adults between June 25, 2004, and July 15, 2008, from ten areas of China, recording alcohol use and other characteristics. It followed them for about 10 years (until Jan 1, 2017), monitoring cardiovascular disease (including ischaemic stroke, intracerebral haemorrhage, and myocardial infarction) by linkage with morbidity and mortality registries and electronic hospital records. 161 498 participants were genotyped for two variants that alter alcohol metabolism, ALDH2-rs671 and ADH1B-rs1229984. Adjusted Cox regression was used to obtain the relative risks associating disease incidence with self-reported drinking patterns (conventional epidemiology) or with genotype-predicted mean male alcohol intake (genetic epidemiology-ie, Mendelian randomisation), with stratification by study area to control for variation between areas in disease rates and in genotype-predicted intake. FINDINGS: 33% (69 897/210 20...