Abstract 1967: Genome-wide Association Analysis of 25,330 Individuals Identifies Multiple Loci Associated With Resting Heart Rate
Introduction: Higher resting heart rate is associated with increased cardiovascular mortality and sudden death, independent of traditional risk factors. Though genetic factors account for up to 26 to 32% of heart rate variation based on family studies, little is known about specific genetic loci involved.
Methods: We performed a prospective meta-analysis of eight genome-wide association studies estimating the association between age-, sex-, and body mass index-adjusted RR interval (inverse heart rate) and ~2.5 million autosomal SNPs. The sample comprised individuals of European descent with genome-wide genotype data. Individuals were excluded for prevalent myocardial infarction, heart failure, atrial fibrillation, 2nd or 3rd degree atrio-ventricular block, current use of β-blocker therapy, non-dihydropyridine calcium antagonists or digoxin, or heart rate less than 50 or greater than 100 beats per minute. Additional association evidence for selected loci was sought in individuals from 5 independent cohorts of European ancestry.
Results: Meta-analysis of genome-wide association study results from a total of 25,330 individuals and replication results from 9,299 individuals showed novel genome-wide significant association in four loci:3q26 GNB4 (P =4.3×10 – 8), 6q22 SLC35F1 near PLN (P =2.5×10 –9), 12p12 near BCAT1 (P =2.5×10 –9), 14q12 MYH6 (P =4.8×10 –12) and replicated an association recently reported in Asians at 6q22 near GJA1 (P =8.7×10 –15). We also found support for an additional heart rate locus reported in Asians at 1q32 C1orf132 (P =4.5×10 –5).
Conclusion: In this genome-wide association study for resting heart rate, four novel associated loci were identified and two recently reported loci were replicated. These findings offer the promise of an improved understanding of the genetic determinants of heart rate and point toward genes/variants that could be tested for an influence on cardiovascular mortality risk.