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

Abstract

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). SB was considered as an important risk factor of HF. 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. 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. This MR study identified that increased TV screen time may predispose individuals to the development of HF.