Resting heart rate and incident atrial fibrillation: A stratified Mendelian randomization in the AFGen consortium

J E Siland, B Geelhoed, C Roselli, B Wang, H J Lin, S Weiss, S Trompet, M E van den Berg, E Z Soliman, L Y Chen, I Ford, J W Jukema, P W Macfarlane, J Kornej, H Lin, K L Lunetta, M Kavousi, J A Kors, M A Ikram, X Guo, J Yao, M Dörr, S B Felix, U Völker, N Sotoodehnia, D E Arking, B H Stricker, S R Heckbert, S A Lubitz, E J Benjamin, A Alonso, P T Ellinor, P van der Harst and M Rienstra

PLOS ONE, 2022, vol. 17, issue 5, 1-13

Abstract: Background: Both elevated and low resting heart rates are associated with atrial fibrillation (AF), suggesting a U-shaped relationship. However, evidence for a U-shaped causal association between genetically-determined resting heart rate and incident AF is limited. We investigated potential directional changes of the causal association between genetically-determined resting heart rate and incident AF. Method and results: Seven cohorts of the AFGen consortium contributed data to this meta-analysis. All participants were of European ancestry with known AF status, genotype information, and a heart rate measurement from a baseline electrocardiogram (ECG). Three strata of instrumental variable-free resting heart rate were used to assess possible non-linear associations between genetically-determined resting heart rate and the logarithm of the incident AF hazard rate: 75 beats per minute (bpm). Mendelian randomization analyses using a weighted resting heart rate polygenic risk score were performed for each stratum. Conclusions: For resting heart rates below 65 bpm, our results support an inverse causal association between genetically-determined resting heart rate and incident AF.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0268768

DOI: 10.1371/journal.pone.0268768

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