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首页> 外文期刊>Human Molecular Genetics >Pancreatic beta-cell function and type 2 diabetes risk: Quantify the causal effect using a Mendelian randomization approach based on meta-analyses
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Pancreatic beta-cell function and type 2 diabetes risk: Quantify the causal effect using a Mendelian randomization approach based on meta-analyses

机译：胰腺β细胞功能和2型糖尿病风险：使用基于Meta分析的孟德尔随机化方法量化因果关系

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The objective of the study is to quantify the causal effect of β-cell function on type 2 diabetes by minimizing residual confounding and reverse causation. We employed a Mendelian randomization (MR) approach using TCF7L2 variant rs7903146 as an instrument for lifelong levels of β-cell function. We first conducted two sets of meta-analyses to quantify the association of the TCF7L2 variant with the risk of type 2 diabetes among 55 436 cases and 106 020 controls from 66 studies by calculating pooled odds ratio (OR) and to quantify the associations with multiple direct or indirect measures of β-cell function among 35 052 non-diabetic individuals from 31 studies by calculating pooled mean difference. We further applied the method of MR to obtain the causal estimates for the effect of β-cell function on type 2 diabetes risk based on findings from the meta-analyses. The OR [95% confidence interval (CI)] was 0.87 (0.81-0.93) for each five unit increment in homeostasis model assessment of insulin secretion (HOMA-%B) (P = 3.0 × 10 -5). In addition, for measures based on intravenous glucose tolerance test, ORs (95% CI) associated with type 2 diabetes risk were 0.24 (0.08-0.74) (P = 0.01) and 0.14 (0.04-0.48) (P = 0.002) for per 1 standard deviation increment in insulin sensitivity index and disposition index, respectively. Findings from the present study lend support to a causal role of pancreatic β-cell function itself in the etiology of type 2 diabetes.
机译：该研究的目的是通过最小化残留混杂和反向因果关系来量化β细胞功能对2型糖尿病的因果关系。我们采用孟德尔随机化（MR）方法，使用TCF7L2变体rs7903146作为终生β细胞功能水平的工具。我们首先进行了两组荟萃分析，通过计算汇总比值比（OR）来量化55 436例病例和106 020例对照中的TCF7L2变异与2型糖尿病风险的关联，并通过定量比对来量化关联。通过计算合并均值差，直接或间接测量31个研究中的35 052名非糖尿病患者的β细胞功能。基于荟萃分析的结果，我们进一步应用MR方法来获得β细胞功能对2型糖尿病风险的因果估计。在胰岛素分泌稳态模型评估（HOMA-％B）中，每增加5个单位，OR [95％置信区间（CI）]为0.87（0.81-0.93）（P = 3.0×10 -5）。此外，对于基于静脉葡萄糖耐量试验的措施，与2型糖尿病风险相关的OR（95％CI）为0.24（0.08-0.74）（P = 0.01）和0.14（0.04-0.48）（P = 0.002）胰岛素敏感性指数和处置指数分别增加1个标准差。本研究的发现支持胰腺β细胞功能本身在2型糖尿病病因中的因果作用。

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