title: Identification of genomic loci associated with resting heart rate and shared genetic predictors with all-cause mortality.
abstract: Resting heart rate is a heritable trait correlated with life span. Little is known about the genetic contribution to resting heart rate and its relationship with mortality. We performed a genome-wide association discovery and replication analysis starting with 19.9 million genetic variants and studying up to 265,046 individuals to identify 64 loci associated with resting heart rate (P < 5 × 10-8); 46 of these were novel. We then used the genetic variants identified to study the association between resting heart rate and all-cause mortality. We observed that a genetically predicted resting heart rate increase of 5 beats per minute was associated with a 20% increase in mortality risk (hazard ratio 1.20, 95% confidence interval 1.11-1.28, P = 8.20 × 10-7) translating to a reduction in life expectancy of 2.9 years for males and 2.6 years for females. Our findings provide evidence for shared genetic predictors of resting heart rate and all-cause mortality.
authors: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
authors: Ruben N
authors: RN
authors: Eppinga
authors: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
authors: Yanick
authors: Y
authors: Hagemeijer
authors: Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
authors: Stephen
authors: 0000-0001-5365-8760
authors: S
authors: Burgess
authors: 23andMe, Inc., Mountain View, California, USA.
authors: David A
authors: DA
authors: Hinds
authors: deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.|Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
authors: Kari
authors: K
authors: Stefansson
authors: deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.|School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
authors: Daniel F
authors: 0000-0002-5222-9857
authors: DF
authors: Gudbjartsson
authors: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
authors: Dirk J
authors: DJ
authors: van Veldhuisen
authors: Department of Clinical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.|NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK.
authors: Patricia B
authors: PB
authors: Munroe
authors: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
authors: Niek
authors: 0000-0002-4303-7685
authors: N
authors: Verweij
authors: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.|University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.|Durrer Center for Cardiogenetic Research, Netherlands Heart Institute, Utrecht, the Netherlands.
authors: Pim
authors: P
authors: van der Harst
mesh_terms: D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study; D023281:Genomics / Q000379:methods*; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D012146:Rest / Q000502:physiology*; D012307:Risk Factors; D015996:Survival Rate