Exploring the Genetic Roles of Diet and Other Modifiable Risk Factors in the Risk of Angina: A Causal Investigation Using Mendelian Randomization in UK Biobank and FinnGen Cohorts

Abstract

Background: Angina pectoris, a debilitating manifestation of coronary artery disease, has been associated with various modifiable risk factors. However, the causal underpinnings of these associations remain unclear. This study leveraged Mendelian randomization (MR) to investigate the causal roles of dietary patterns, smoking behaviors, body mass index (BMI), and physical activity in the development of angina. Methods: Two-sample MR analyses were performed using summary-level data from large-scale genome-wide association studies (GWASs) and biobank resources, including the UK Biobank (UKB) and FinnGen cohorts. Genetic variants associated with various types of exposure such as fruit and salad intake, smoking initiation and intensity, BMI, and physical activity were used as instrumental variables, and their causal effects on angina risk were assessed. Results: In the UKB cohort (336,683 individuals, 10,618 cases), genetically proxied fruit (OR = 0.95, 95% CI: 0.93–0.97) and cheese intake (OR = 0.98, 95% CI: 0.97–0.99) were associated with decreased angina risk, while smoking initiation (OR = 1.01, 95% CI: 1.002–1.012), maternal smoking (OR = 1.06, 95% CI: 1.03–1.09), and BMI (OR = 1.01, 95% CI: 1.01–1.02) were associated with increased risk. In the FinnGen cohort (206,008 individuals, 18,168 cases), fruit (OR = 0.30, 95% CI: 0.17–0.53) and salad intake (OR = 0.31, 95% CI: 0.12–0.55) were found to be protective, while smoking initiation (OR = 1.20, 95% CI: 1.04–1.37) and intensity (OR = 1.15, 95% CI: 1.04–1.26) and BMI (OR = 1.31, 95% CI: 1.18–1.47) increased angina risk. Conclusions: This study provides robust evidence for the causal roles of various modifiable risk factors associated with angina development, highlighting the potential benefits of dietary interventions that promote increased fruit and vegetable consumption, smoking cessation, and weight management to mitigate angina risk. Further investigation is needed to generalize these findings to populations with diverse genetic backgrounds, lifestyles, and environmental exposures.