Gestational diabetes and future cardiovascular diseases: associations by sex-specific genetic data

作者：Yeshen Zhang, Shijie Yu, Z. J. Chen, H. M. Liu, Huixian Li, Xinyang Long, Fei Ye, Wenzhi Luo, Yining Dai, Shan Tu, Weikun Chen, Siyu Kong, Yu He, Ling Xue, Ning Tan, Huiying Liang, Zhihui Zhang, Pengcheng He, Chongyang Duan, Yuanhui Liu · 发表于：European Heart Journal · 年份：2024 · DOI：10.1093/eurheartj/ehae706 · 被引用次数：27 · 研究领域：Gestational Diabetes Research and Management、Genetic Associations and Epidemiology、Pregnancy and preeclampsia studies

BACKGROUND AND AIMS: Observational studies have highlighted that gestational diabetes mellitus is associated with a higher risk of cardiovascular diseases, but the causality remains unclear. Herein, the causality between genetic predisposition to gestational diabetes mellitus and the risk of cardiovascular diseases was investigated using sex-specific Mendelian randomization analysis. METHODS: Linkage disequilibrium score regression analysis and two-sample Mendelian randomization analysis were applied to infer the genetic correlation and causality, respectively. Mediation analysis was conducted using a two-step Mendelian randomization approach. Sensitivity analyses were performed to differentiate causality from pleiotropy. The genome-wide association study summary statistics for gestational diabetes mellitus were obtained from FinnGen consortium, while for cardiovascular diseases were generated based on individual-level genetic data from the UK Biobank. RESULTS: Linkage disequilibrium score regression analyses revealed that gestational diabetes mellitus had a significant genetic correlation with coronary artery disease and myocardial infarction after Benjamini-Hochberg correction in ever-pregnant women. In Mendelian randomization analyses, odds ratios (95% confidence interval) for coronary artery disease and myocardial infarction were 1.09 (1.01-1.17) and 1.12 (.96-1.31) per unit increase in the log-odds of genetic predisposition to gestational diabetes mellitus in ever-pregna...