Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Department of Epidemiology & Biostatistics, School of Public Health, Southeast University, Nanjing 210009, China.
Department of Cardiology, Zhong Da Hospital, Southeast University, Nanjing 210009, China.
Nutrients. 2022 Apr 29;14(9):1878. doi: 10.3390/nu14091878.
Although observational studies have shown positive associations between body mass index (BMI) and the risk of atrial fibrillation (AF), the causal relationship is still uncertain owing to the susceptibility to confounding and reverse causation. This study aimed to examine the potential causality of BMI on AF by conducting a two-sample Mendelian randomization (TSMR) study.
The independent genetic variants associated with BMI ( = 303) at the genome-wide significant level were derived as instrumental variables (IV) from the Genetic Investigation of Anthropometric Traits (GIANT) consortium consisting of 681,275 individuals of European ancestry. We then derived the outcome data from a GWAS meta-analysis comprised of 60,620 cases and 970,216 controls of European ancestry. The TSMR analyses were performed in five methods, namely inverse variance weighted (IVW) method, MR-Egger regression, the weighted median estimator (WME), the generalized summary data-based Mendelian randomization (GSMR), and the robust adjusted profile score (RAPS), to investigate whether BMI was causally associated with the risk of AF.
We found a genetically determined 1-standard deviation (SD) increment of BMI causally increased a 42.5% risk of AF (OR = 1.425; 95% CI, 1.346 to 1.509) based on the IVW method, which was consistent with the results of MR-Egger regression, WME, GSMR, as well as RAPS. The Mendelian randomization assumptions did not seem to be violated.
This study provides evidence that higher BMI causally increased the risk of AF, suggesting control of BMI and obesity for prevention of AF.
目的：本研究旨在通过双样本 Mendelian 随机化（TSMR）研究来检验 BMI 与房颤（AF）风险之间的潜在因果关系。
方法：从包含 681275 名欧洲血统个体的遗传特征与人体测量学研究（GIANT）联盟中，获得与 BMI（=303）相关的全基因组显著水平的独立遗传变异作为工具变量（IV）。然后，我们从包含 60620 例病例和 970216 例欧洲血统对照的 GWAS 荟萃分析中得出结果数据。我们采用了 5 种方法（即逆方差加权法、MR-Egger 回归、加权中位数估计法、广义汇总数据 Mendelian 随机化法和稳健调整轮廓评分法）进行 TSMR 分析，以研究 BMI 是否与 AF 风险存在因果关系。
结果：基于逆方差加权法，我们发现遗传决定的 BMI 增加 1 个标准差（SD）会导致 AF 风险增加 42.5%（OR=1.425；95%CI，1.346 至 1.509），这与 MR-Egger 回归、加权中位数估计法、广义汇总数据 Mendelian 随机化法以及稳健调整轮廓评分法的结果一致。Mendelian 随机化假设似乎没有被违反。
结论：本研究提供了证据表明，较高的 BMI 会导致 AF 的风险增加，这表明控制 BMI 和肥胖可能有助于预防 AF。
