Resting heart rate causally affects the brain cortical structure: Mendelian randomization study

Abstract Resting heart rate (RHR) has been linked to impaired cortical structure in observational studies. However, the extent to which this association is potentially causal has not been determined. Using genetic data, this study aimed to reveal the causal effect of RHR on brain cortical structure. A Two-Sample Mendelian randomization (MR) analysis was conducted. Sensitivity analyses, weighted median, MR Pleiotropy residual sum and outlier, and MR-Egger regression were conducted to evaluate heterogeneity and pleiotropy. A causal relationship between RHR and cortical structures was identified by MR analysis. On the global scale, elevated RHR was found to decrease global surface area (SA; P < 0.0125). On a regional scale, the elevated RHR significantly decreased the SA of pars triangularis without global weighted (P = 1.58 × 10−4) and the thickness (TH) of the paracentral with global weighted (P = 3.56 × 10−5), whereas it increased the TH of banks of the superior temporal sulcus in the presence of global weighted (P = 1.04 × 10−4). MR study provided evidence that RHR might be causally linked to brain cortical structure, which offers a different way to understand the heart–brain axis theory.