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

Author

Listed:
  • 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
  • M Rienstra

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.

Suggested Citation

  • 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 Kav, 2022. "Resting heart rate and incident atrial fibrillation: A stratified Mendelian randomization in the AFGen consortium," PLOS ONE, Public Library of Science, vol. 17(5), pages 1-13, May.
    • Handle: RePEc:plo:pone00:0268768
    DOI: 10.1371/journal.pone.0268768
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