孟德尔随机化
2型糖尿病
脂肪组织
医学
体质指数
优势比
置信区间
内科学
体脂百分比
人体测量学
糖尿病
内分泌学
生理学
生物
遗传学
基因型
遗传变异
基因
作者
Yijie Zhu,Qi Wang,Huajie Dai,Tianzhichao Hou,Tiange Wang,Zhiyun Zhao,Mian Li,Mengping Wei,Jian Yang,Jieli Lu,Yu Xu,Yuhong Chen,Guang Ning,Jie Zheng,Yufang Bi,Min Xu,Weiqing Wang
摘要
Abstract Aim To investigate the sex‐specific causality of body compositions in type 2 diabetes and related glycaemic traits using Mendelian randomization (MR). Materials and Methods We leveraged sex‐specific summary‐level statistics from genome‐wide association studies for three adipose deposits adjusted for body mass index and height, including abdominal subcutaneous adipose tissue, visceral adipose tissue (VATadj) and gluteofemoral adipose tissue (GFATadj), measured by MRI (20 038 women; 19 038 men), and fat mass‐adjusted appendicular lean mass (ALMadj) (244 730 women; 205 513 men) in the UK Biobank. Sex‐specific statistics of type 2 diabetes were from the Diabetes Genetics Replication and Meta‐analysis Consortium and those for fasting glucose and insulin were from the Meta‐analyses of Glucose and Insulin‐related Traits Consortium. Univariable and multivariable MR (MVMR) were performed. We also performed MR analyses of anthropometric traits and genetic association analyses using individual‐level data of body composition as validation. Results Univariable MR analysis showed that, in women, higher GFATadj and ALMadj exerted a causally protective effect on type 2 diabetes (GFATadj: odds ratio [OR] 0.59, 95% confidence interval [CI; 0.50, 0.69]; ALMadj: OR 0.84, 95% CI [0.77, 0.91]) and VATadj to be riskier in glycaemic traits. MVMR showed that GFATadj retained a robust effect on type 2 diabetes (OR 0.57, 95% CI [0.42, 0.77]; P = 2.6 × 10 −4 ) in women, while it was nominally significant in men (OR 0.58, 95% CI [0.35, 0.96]; P = 3.3 × 10 −2 ), after adjustment for ASATadj and VATadj. MR analyses of anthropometric measures and genetic association analyses of glycaemic traits confirmed the results. Conclusions Body composition has a sex‐specific effect on type 2 diabetes, and higher GFATadj has an independent protective effect on type 2 diabetes in both sexes.
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