Identifying the causal relationship between sedentary behavior and heart failure: Insights from a Mendelian randomization study and mediation analysis

Abstract

Background: Observational studies have revealed that a lack of physical exercise may be linked to a higher risk of heart failure (HF). Here, the causal relationship between sedentary behavior (SB) and HF was investigated using Mendelian randomization (MR). Hypothesis: SB was considered as an important risk factor of HF. Methods: Single nucleotide polymorphisms with a genome-wide statistical significance threshold of <5 × 10−8 among the SB-proxied phenotypes (TV screen time, computer use, and driving) from genome-wide association study (GWAS) datasets were identified as instrumental variables (IVs). The MR study was performed using the inverse-variance weighting (IVW) model as a primary standard to evaluate causal relationships. Simultaneously, MR-Egger regression, weighted median, and maximum likelihood models were used as supplements. Sensitivity analysis, consisting of a heterogeneity and horizontal pleiotropy test, was performed using Cochran's Q, MR-Egger intercept, and MR-PRESSO tests to ensure the reliability of conclusions. Results: The IVW model results showed that increased TV screen time correlated with a higher genetic susceptibility for HF in both HF-associated GWAS datasets, which was also supported by weighted median and maximum likelihood model results. The odds ratios with 95% confidence intervals were 1.418 (1.182–1.700) and 1.486 (1.136–1.943), respectively. Although the results of Cochran's Q test indicated certain heterogeneity among the IVs. The MR-Egger intercept and MR-PRESSO tests suggested no horizontal pleiotropy and verified the reliability of the conclusion. Conclusions: This MR study identified that increased TV screen time may predispose individuals to the development of HF.