Examining Casual Associations Between Sedentary Time And Heart Failure: A Two-sample Mendelian Randomization Analysis

Previous observational studies have shown a significant association between excess sedentary time (ST) and the incidence risk of heart failure (HF) in general population. However, causal pathway linking between ST and HF remains poorly understood. PURPOSE: The objective of this study was to assess the causal relationship between ST and HF using the two-sample Mendelian Randomization (MR). METHODS: The present MR used genetic instruments identified for self-reported ST extracted from a meta-analysis of 51 genome wide association studies (GWAS), encompassing data from 703,901 individuals. The GWAS identified 89 independent single nucleotide polymorphisms (SNPs) in 88 loci that were associated with leisure screen time. Outcomes included HF data extracted from the Heart Failure Molecular Epidemiology for Therapeutic Targets (HERMES) Consortium, which were identified through a different meta-analysis of GWAS. This GWAS identified 12 independent SNPs in 11 loci that were associated with HF based on 47,309 cases and 930,014 controls. There were a total of 108 exposure SNPs used in the MR analysis. Univariate MR estimates were obtained using various methods such as inverse variance weighted (IVW), MR-Egger, and weighted median. RESULTS: The results from univariate MR analysis showed significant causal link of ST with the increased risk of HF (OR = 1.14; 95% CI = 1.06, 1.22; P < 0.01 from the IVW method). However, this causal association was not supported when utilizing different estimation method (Ps >0.05). CONCLUSIONS: Our findings support previous evidence suggesting an association between ST and incident HF. However, caution is needed as the nonsignficant causal links estimated by MR-Egger and weighted median may be due to heterogeneity or pleiotropy. Further studies are needed with HF subtypes (HFpEF, HFrEF), and with other measures of ST. Table. - Mendelian Randomization Statistical Methods and Odds Ratios Method Odds Ratio 95% CI P-value MR Egger 1.08 0.77, 1.39 0.63 Weighted median 1.07 0.97, 1.17 0.16 Inverse variance weighted (IVW) 1.14 1.06, 1.22 <0.01* Simple mode 1.04 0.77, 1.31 0.78 Weighted mode 1.05 0.83, 1.27 0.69 CI confidence interval; *Indicates significance