Causal association of modifiable factors with cardiometabolic multimorbidity: an exposome-wide Mendelian randomization investigation

作者：Dun Li, Jing Lin, Hongxi Yang, Lihui Zhou, Yujian Li, Zhe Xu, Li Sun, Xinyu Zhang, Weili Xu, Yaogang Wang · 发表于：Cardiovascular Diabetology · 年份：2025 · DOI：10.1186/s12933-025-02790-w · 被引用次数：23 · 研究领域：Genetic Associations and Epidemiology、Chronic Disease Management Strategies、Health, Environment, Cognitive Aging

Cardiometabolic multimorbidity (CMM), characterized by the co-existence of two or more cardiometabolic diseases (CMDs) including type 2 diabetes (T2D), coronary artery disease (CAD), and stroke, persists as a global health challenge. However, the causal associations of modifiable factors with CMDs and CMM remains to be systematically investigated. In this study, a three-stage design Mendelian randomization (MR) investigation was conducted, using two-sample MR with potential sample overlap correction and multiple testing, multivariable MR analysis, and multi-response MR, with modifiable factors covering domains of socioeconomic factors, behavioral factors, biochemical factors, and physical measures as exposures, and CMM and CMDs as outcomes. Updated large-scale genome-wide association study (GWAS) data based on systematic collection from GWAS Catalog were applied. Our major findings suggested that, 13 of 23 modifiable factors across four domains, including educational attainment (odds ratio: 0.858, 95% confidence interval: 0.834–0.883), household income (0.794, 0.720–0.875), lifetime smoking behavior (1.201, 1.145–1.260), leisure screen time (1.255, 1.186–1.327), low-density lipoprotein cholesterol levels (1.062, 1.046–1.079), total cholesterol levels (1.045, 1.029–1.062), Apolipoprotein B (1.035, 1.019–1.051), fasting glucose (1.096, 1.038–1.157), glycated hemoglobin (HbA1c) (1.062, 1.037–1.089), systolic blood pressure (1.125, 1.104–1.146), diastolic blood pressure (1.104, 1...