Zhang Yanan, Wang Ruiqing, Tang Xinhua, Wang Yanjun, Guo Ping, Wang Shukang, Liu Jing
Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China.
Department of Hematology, Qilu Hospital of Shandong University, Jinan, China.
Front Genet. 2022 Mar 29;13:835917. doi: 10.3389/fgene.2022.835917. eCollection 2022.
The association reported between tea intake and type 2 diabetes (T2D) is inconsistent in previous studies and remains controversial. We aimed to explore the causal relationship between tea intake, T2D, and glycemic traits including hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), fasting serum insulin (FSI), and homeostasis model of insulin resistance (HOMA-IR) levels. A 2-sample Mendelian randomization (MR) was performed using summary statistics from large-scale genome-wide association studies of tea intake from the UK Biobank, T2D from the DIAGRAM consortium, and glycemic traits from the Magic consortium. The findings were verified through sensitivity analyses using various MR methods with different model assumptions and by comprehensively evaluating the influence of pleiotropy effects and outliers. With the use of a two-sample MR with inverse variance-weighted method, the odds ratio per unit SD change of tea intake (SD: 2.85 cups/day) for T2D, HbA1c, FPG, FSI, and HOMA-IR levels was 0.949 (95% CI 0.844-1.067, = 0.383), 0.994 (95% CI 0.975-1.013, = 0.554), 0.996 (95% CI 0.978-1.015, = 0.703), 0.968 (95% CI 0.948-0.986, = 0.001), and 0.953 (95% CI 0.900-1.009, = 0.102), respectively. The results were consistent with those of the other six methods that we used with different model assumptions, suggesting that the findings were robust and convincing. We also performed various sensitivity analyses for outlier removal, pleiotropy detection, and leave-one-out analysis. Our MR results did not support the causal effect of tea intake on T2D and crucial glycemic traits. These findings suggest that previous observational studies may have been confounded.
先前研究中报道的茶摄入量与2型糖尿病（T2D）之间的关联并不一致，仍存在争议。我们旨在探讨茶摄入量、T2D以及包括糖化血红蛋白（HbA1c）、空腹血糖（FPG）、空腹血清胰岛素（FSI）和胰岛素抵抗稳态模型（HOMA-IR）水平在内的血糖特征之间的因果关系。使用来自英国生物银行的茶摄入量、DIAGRAM联盟的T2D以及Magic联盟的血糖特征的大规模全基因组关联研究的汇总统计数据进行了两样本孟德尔随机化（MR）分析。通过使用具有不同模型假设的各种MR方法进行敏感性分析，并综合评估多效性效应和异常值的影响，对研究结果进行了验证。使用逆方差加权法的两样本MR分析显示，茶摄入量每单位标准差变化（标准差：2.85杯/天）对T2D、HbA1c、FPG、FSI和HOMA-IR水平的比值比分别为0.949（95%可信区间0.844-1.067，P = 0.383）、0.994（95%可信区间0.975-1.013，P = 0.554）、0.996（95%可信区间0.978-1.015，P = 0.703）、0.968（95%可信区间0.948-0.986，P = 0.001）和0.953（95%可信区间0.900-1.009，P = 0.102）。结果与我们使用不同模型假设的其他六种方法的结果一致，表明研究结果具有稳健性和说服力。我们还进行了各种敏感性分析，包括异常值去除、多效性检测和留一法分析。我们的MR结果不支持茶摄入量对T2D和关键血糖特征的因果效应。这些发现表明，先前的观察性研究可能存在混杂因素。
