Dataset Information

Physical activity, sedentary behavior and risk of coronary artery disease, myocardial infarction and ischemic stroke: a two-sample Mendelian randomization study.

ABSTRACT:

Aims

Observational evidence suggests that physical activity (PA) is inversely and sedentarism positively related with cardiovascular disease risk. We performed a two-sample Mendelian randomization (MR) analysis to examine whether genetically predicted PA and sedentary behavior are related to coronary artery disease, myocardial infarction, and ischemic stroke.

Methods and results

We used single nucleotide polymorphisms (SNPs) associated with self-reported moderate to vigorous PA (n = 17), accelerometer based PA (n = 7) and accelerometer fraction of accelerations > 425 milli-gravities (n = 7) as well as sedentary behavior (n = 6) in the UK Biobank as instrumental variables in a two sample MR approach to assess whether these exposures are related to coronary artery disease and myocardial infarction in the CARDIoGRAMplusC4D genome-wide association study (GWAS) or ischemic stroke in the MEGASTROKE GWAS. The study population included 42,096 cases of coronary artery disease (99,121 controls), 27,509 cases of myocardial infarction (99,121 controls), and 34,217 cases of ischemic stroke (404,630 controls). We found no associations between genetically predicted self-reported moderate to vigorous PA, accelerometer-based PA or accelerometer fraction of accelerations > 425 milli-gravities as well as sedentary behavior with coronary artery disease, myocardial infarction, and ischemic stroke.

Conclusions

These results do not support a causal relationship between PA and sedentary behavior with risk of coronary artery disease, myocardial infarction, and ischemic stroke. Hence, previous observational studies may have been biased.

SUBMITTER: Bahls M

PROVIDER: S-EPMC8484185 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Previous studies have indicated that the gut microbiota (GM) is associated with coronary artery disease (CAD), but the causality of these associations remains unestablished due to confounding factors and reverse causality. We conducted Mendelian randomization study (MR) to determine the causal effect of the specific bacterial taxa on CAD/myocardial infarction (MI) and identify the mediating factors involved. Methods: Two-sample MR, multivariable MR (MVMR) and mediation analysis were performed. Inverse-variance weighting (IVW) was the main method used to analyze causality, and sensitivity analysis was used to verify the reliability of the study. Causal estimates from CARDIoGRAMplusC4D and FinnGen databases were combined using the meta-analysis method, and repeated validation was conducted based on the UK Biobank (UKB) database. Confounders that may affect the causal estimates were corrected by MVMP and the potential mediation effects were investigated by using mediation analysis. Results: The study suggested that increased abundance of the RuminococcusUCG010 genus leads to a lower risk of CAD (OR, 0.88; 95% CI, 0.78, 1.00; p = 2.88 × 10-2) and MI (OR, 0.88; 95% CI, 0.79, 0.97; p = 1.08 × 10-2), with consistent results in both meta-analysis (CAD: OR, 0.86; 95% CI, 0.78, 0.96; p = 4.71 × 10-3; MI: OR, 0.82; 95% CI, 0.73, 0.92; p = 8.25 × 10-4) and repeated analysis of the UKB dataset (CAD: OR, 0.99; 95% CI, 0.99, 1.00, p = 2.53 × 10-4; MI: OR, 0.99; 95% CI, 0.99, 1.00, p = 1.85 × 10-11). Based on multiple databases, T2DM was proved as a mediating factor in the causal effect of RuminococcusUCG010 and CAD/MI, with an average mediation effect proportion of 20% on CAD and 17% on MI, respectively. Conclusion: This MR study provided suggestive genetic evidence that the higher the RuminococcusUCG010 abundance is, the lower the risk of CAD and MI, with T2DM playing a mediating effect. This genus may become a novel target in strategies for treating and preventing CAD and MI.