Genome-wide association analysis identifies multip... [Hum Mol Genet. 2010] - PubMed result

Hum Mol Genet. 2010 Jul 16. [Epub ahead of print]

Genome-wide association analysis identifies multiple loci related with resting heart rate.
Eijgelsheim M, Newton-Cheh C, Sotoodehnia N, de Bakker PI, Müller M, Morrison AC, Smith AV, Isaacs A, Sanna S, Dörr M, Navarro P, Fuchsberger C, Nolte IM, de Geus EJ, Estrada K, Hwang SJ, Bis JC, Rückert IM, Alonso A, Launer LJ, Hottenga JJ, Rivadeneira F, Noseworthy PA, Rice KM, Perz S, Arking DE, Spector TD, Kors JA, Aulchenko YS, Tarasov KV, Homuth G, Wild SH, Marroni F, Gieger C, Licht CM, Prineas RJ, Hofman A, Rotter JI, Hicks AA, Ernst F, Najjar SS, Wright AF, Peters A, Fox ER, Oostra BA, Kroemer HK, Couper D, Völzke H, Campbell H, Meitinger T, Uda M, Witteman JC, Psaty BM, Wichmann HE, Harris TB, Kääb S, Siscovick DS, Jamshidi Y, Uitterlinden AG, Folsom AR, Larson MG, Wilson JF, Penninx BW, Snieder H, Pramstaller PP, van Duijn CM, Lakatta EG, Felix SB, Gudnason V, Pfeufer A, Heckbert SR, Stricker BH, Boerwinkle E, O'Donnell CJ.

Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.

Abstract
Higher resting heart rate is associated with increased cardiovascular disease and mortality risk. Though heritable factors play a substantial role in population variation, little is known about specific genetic determinants. This knowledge can impact clinical care by identifying novel factors that influence pathologic heart rate states, modulate heart rate through cardiac structure and function or by improving our understanding of the physiology of heart rate regulation. To identify common genetic variants associated with heart rate we performed a meta-analysis of fifteen genome-wide association studies, including 38,991 subjects of European ancestry, estimating the association between age-,sex-, and body mass-adjusted RR interval (inverse heart rate) and approximately 2.5 million markers. Results with P<5x10(-8) were considered genome-wide significant. We constructed regression models with multiple markers to assess whether results at less stringent thresholds were likely to be truly associated with RR interval. We identified six novel associations with resting heart rate at six loci: 6q22 near GJA1, 14q12 near MYH7, 12p12 near SOX5, c12orf67, BCAT1, LRMP and CASC1, 6q22 near SLC35F1, PLN and c6orf204, 7q22 near SLC12A9, UfSp1 and 11q12 near FADS1. Associations at 6q22 400kb away from GJA1, at 14q12 MYH6 and at 1q32 near CD34 identified in previously published GWAS were confirmed. In aggregate, these variants explain approximately 0.7% of RR interval variance. A multi-variant regression model including 20 variants with P<10(-5) increased explained variance to 1.6% suggesting that some loci falling short of genome-wide significance are likely truly associated. Future research is warranted to elucidate underlying mechanisms that may impact clinical care.

PMID: 20639392 [PubMed - as supplied by publisher]
Genome-wide association analysis identifies multip... [Hum Mol Genet. 2010] - PubMed result