Type II diabetes mellitus (T2DM) is a metabolic disease with high incidence, which has seriously affected human life and health. The associations among waist circumference (WC), waist-to-hip ratio (WHR), and T2DM were discovered in observational studies. However, the causality of these associations still remains unknown. The present study aims to apply two-sample Mendelian randomization (TSMR) using genetic variants as instrumental variables (IVs) to evaluate the causality among WC, WHR, and T2DM. The participants were from three independent studies in genome-wide association studies (GWAS) datasets, which included 127,997 Europeans for WC, 73,137 Europeans for WHR and 659,316 Europeans for T2DM. Furthermore, 16 were associated WC SNPs and eight were associated WHR SNPs as instrument variables were selected for TSMR using P < 5 × 10^–8 standard. The pooled odd ratios (ORs) for the assessment of higher WC and WHR on the risk of T2DM for these SNPs were calculated using inverse variance weighted (IVW) method, and validated through extensively complementary analyses. The OR for T2DM per SD (cm) higher WC was 2.623 (95% CI 2.286–3.010, P = 5.000E−43), and the OR for T2DM per SD (cm) higher WHR was 1.751 (95% CI 1.122–2.733, P = 0.014). Consistent results for other methods were obtained. Furthermore, the range of OR fluctuation between WC and T2DM was from 2.623 to 2.986, while that between WHR and T2DM was from 0.990 to 2.931. Overall, these present results provide genetic support that suggests that the use of TSMR, and higher WC and WHR increased the T2DM risk among the European population.

II型糖尿病（T2DM）是一种高发的代谢性疾病，已严重影响人类的生命和健康。在观察性研究中发现了腰围（WC），腰臀比（WHR）和T2DM之间的关联。但是，这些关联的因果关系仍然未知。本研究旨在应用两样本孟德尔随机化（TSMR），使用遗传变异作为工具变量（IVs）评估WC，WHR和T2DM之间的因果关系。参与者来自全基因组关联研究（GWAS）数据集中的三项独立研究，其中包括127,997例WC的欧洲人，73,137例WHR的欧洲人和659,316例T2DM的欧洲人。此外，使用TSMR选择仪器变量时，有16个相关的WC SNP和8个相关的WHR SNP。P  <5×10 ^–8标准。使用逆方差加权（IVW）方法计算用于评估这些SNP的较高WC和WHR的T2DM风险的合并奇数比（OR），并通过广泛的补充分析进行验证。T2DM每SD（cm）较高的WC的OR为2.623（95％CI 2.286–3.010，P  = 5.000E-43），而W2HR每SD（cm）较高的WHR为1.751（95％CI 1.122–2.733） ，P = 0.014）。获得了其他方法的一致结果。此外，WC和T2DM之间的OR波动范围为2.623至2.986，而WHR和T2DM之间的OR波动范围为0.990至2.931。总体而言，这些目前的结果提供了遗传支持，表明使用TSMR以及较高的WC和WHR会增加欧洲人群中T2DM的风险。