A mendelian randomization study in the UK suggested that a genetic predisposition to higher waist-to-hip ratio (WHR) adjusted for body mass index (BMI) was associated with increased risk of type 2 diabetes (T2D) and coronary heart disease (CHD). A polygenic risk score for WHR adjusted for BMI, a measure of genetic predisposition to abdominal adiposity, was constructed with 48 single-nucleotide polymorphisms. The association of this score with cardiometabolic traits, T2D, and CHD was tested in a mendelian randomization analysis that combined case-control and cross-sectional data sets from 2007 to 2015. Among 111 986 individuals in the UK Biobank, the mean age was 57 (SD, 8) years, 58 845 participants (52.5%) were women, and mean WHR was 0.875. Analysis of summary-level genome-wide association study results and individual-level UK Biobank data demonstrated that a 1-SD increase in WHR adjusted for BMI mediated by the polygenic risk score was associated with 27-mg/dL higher triglyceride levels, 4.1-mg/dL higher 2-hour glucose levels, and 2.1–mm Hg higher systolic blood pressure. A 1-SD genetic increase in WHR adjusted for BMI was also associated with a higher risk of T2D (odds ratio, 1.77; absolute risk increase per 1000 participant-years, 6.0; number of participants with T2D outcome, 40 530) and CHD (odds ratio, 1.46; absolute risk increase per 1000 participant-years, 1.8; number of participants with CHD outcome, 66 440). The findings provide evidence supportive of a causal association between abdominal adiposity and T2D and CHD. Source: http://jamanetwork.com/
英国的孟德尔随机研究表明，经体重指数校正的遗传性腰臀比较高与2型糖尿病和冠心病的风险增加相关。利用48个单核苷酸多态性构建了经体重指数校正的多基因风险评分，作为对腹部肥胖遗传易感性的指标。对该评分与心脏代谢状态，2型糖尿病和冠心病的关系在2007年至2015年的组合病例对照及横断面数据库的孟德尔随机分析中进行了测试。在英国生物银行的111986个个体中，平均年龄是57（标准差，8）岁，58845名参与者（52.5％）是女性，平均腰臀比为0.875。总体水平全基因组相关研究结果和个体水平英国生物库数据的分析表明，经体重指数校正的多基因风险评分所致腰臀比1-标准差的增加，与甘油三酯水平增加27毫克/分升， 2小时葡萄糖水平增加4.1毫克/分升和收缩压增加2.1毫米汞柱相关。经体重指数校正的遗传性腰臀比1-标准差的增加也与更高的2型糖尿病（风险比，1.77; 每1000个参与者年的绝对风险增加，6.0; 发生糖尿病参与者的数量，40530）和冠心病（风险比，1.46; 每1000个参与者年的绝对风险增加，1.8; 发生冠心病参与者的数量，66440）风险相关。这些发现为支持腹部肥胖与2型糖尿病和冠心病之间的因果关系提供了证据。来源：http://jamanetwork.com/
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