Sex-specific and polygenic effects underlying resting heart rate and associated risk of cardiovascular disease.

Autor:	Nordeidet AN; Cardiac Exercise Research Group (CERG), Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Prinsesse Kristinas gate 3, 7030 Trondheim, Norway., Klevjer M; Cardiac Exercise Research Group (CERG), Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Prinsesse Kristinas gate 3, 7030 Trondheim, Norway.; Department of Cardiology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway., Øvretveit K; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway., Madssen E; Department of Cardiology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway., Wisløff U; Cardiac Exercise Research Group (CERG), Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Prinsesse Kristinas gate 3, 7030 Trondheim, Norway.; Centre for Research on Exercise, Physical Activity and Health, School of Human Movement and Nutrition Sciences, University of Queensland, St. Lucia, Brisbane, Queensland, Australia., Brumpton BM; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway., Bye A; Cardiac Exercise Research Group (CERG), Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Prinsesse Kristinas gate 3, 7030 Trondheim, Norway.; Department of Cardiology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Jazyk:	angličtina
Zdroj:	European journal of preventive cardiology [Eur J Prev Cardiol] 2024 Sep 20; Vol. 31 (13), pp. 1585-1594.
DOI:	10.1093/eurjpc/zwae092
Abstrakt:	Aims: Resting heart rate (RHR) is associated with cardiovascular disease (CVD) and mortality. This study aimed to identify genetic loci associated with RHR, develop a genome-wide polygenic risk score (PRS) for RHR, and assess associations between the RHR PRS and CVD outcomes, to better understand the biological mechanisms linking RHR to disease. Sex-specific analyses were conducted to potentially elucidate different pathways between the sexes. Methods and Results: We performed a genome-wide meta-analysis of RHR (n = 550 467) using two independent study populations, The Trøndelag Health Study (HUNT) and the UK Biobank (UKB), comprising 69 155 and 481 312 participants, respectively. We also developed a genome-wide PRS for RHR using UKB and tested for association between the PRS and 13 disease outcomes in HUNT. We identified 403, 253, and 167 independent single nucleotide polymorphisms (SNPs) significantly associated with RHR in the total population, women, and men, respectively. The sex-specified analyses indicated differences in the genetic contribution to RHR and revealed loci significantly associated with RHR in only one of the sexes. The SNPs were mapped to genes enriched in heart tissue and cardiac conduction pathways, as well as disease-pathways, including dilated cardiomyopathy. The PRS for RHR was associated with increased risk of hypertension and dilated cardiomyopathy, and decreased risk of atrial fibrillation. Conclusion: Our findings provide insight into the pleiotropic effects of the RHR variants, contributing towards an improved understanding of mechanisms linking RHR and disease. In addition, the sex-specific results might contribute to a more refined understanding of RHR as a risk factor for the different diseases. Competing Interests: Conflict of interest: None declared. (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)
Databáze:	MEDLINE
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