An Exploration of Shared Risk Factors for Coronary Artery Disease and Cancer from 109 Traits: The Evidence from Two-Sample Mendelian Randomization Studies

Abstract

Background: Although observational studies have reported several common biomarkers related to coronary artery disease (CAD) and cancer, there is a shortage of traditional epidemiological data to establish causative linkages. Thus, we conducted a comprehensive two-sample Mendelian randomization (MR) analysis to systematically investigate the causal associations of 109 traits with both CAD and cancer to identify their shared risk and protective factors. Methods: The genetic association datasets pertaining to exposure and outcomes were reviewed using the most recent and public genome-wide association studies (GWAS). Inverse variance weighting (IVW), weighted median (WM), and MR-Egger strategies were implemented for the MR analyses. The heterogeneity and pleiotropy were measured utilizing leave-one-out sensitivity testing, MR-PRESSO outlier detection, and Cochran’s Q test. Results: The IVW analyses revealed that genetic-predicted mean sphered cell volume (MSCV) is a protective factor for CAD, and weight is a risk factor. MSCV and weight also show similar effects on cancer. Furthermore, our study also identified a set of risk and protective factors unique to CAD and cancer, such as telomere length. Conclusions: Our Mendelian randomization study sheds light on shared and unique risk and protective factors for CAD and cancer, offering valuable insights that could guide future research and the development of personalized strategies for preventing and treating these two significant health issues.

Keywords

• coronary artery disease
• cancer
• shared risk factor
• mendelian randomization
• uk biobank