Resting heart rate and risk of dementia: a Mendelian randomization study in the international genomics of Alzheimer’s Project and UK Biobank

Abstract

Background Observational studies have demonstrated that a higher resting heart rate (RHR) is associated with an increased risk of dementia. However, it is not clear whether the association is causal. This study aimed to determine the causal effects of higher genetically predicted RHR on the risk of dementia. Methods We performed a two-sample Mendelian randomization analysis to investigate the causal effect of higher genetically predicted RHR on Alzheimer’s disease (AD) using summary statistics from genome-wide association studies. The generalized summary Mendelian randomization (GSMR) analysis was used to analyze the corresponding effects of RHR on following different outcomes: 1) diagnosis of AD (International Genomics of Alzheimer’s Project), 2) family history (maternal and paternal) of AD from UK Biobank, 3) combined meta-analysis including these three GWAS results. Further analyses were conducted to determine the possibility of reverse causal association by adjusting for RHR modifying medication. Results The results of GSMR showed no significant causal effect of higher genetically predicted RHR on the risk of AD (βGSMR = 0.12, P = 0.30). GSMR applied to the maternal family history of AD (βGSMR = −0.18, P = 0.13) and to the paternal family history of AD (βGSMR = −0.14, P = 0.39) showed the same results. Furthermore, the results were robust after adjusting for RHR modifying drugs (βGSMR = −0.03, P = 0.72). Conclusion Our study did not find any evidence that supports a causal effect of RHR on dementia. Previous observational associations between RHR and dementia are likely attributed to the correlation between RHR and other cardiovascular diseases.

Keywords

• Dementia
• Alzheimer’s disease
• Resting heart rate
• Genetic variants
• Mendelian randomization