Published Online
on March 1, 2004

A more recent version of this article appeared on May 1, 2004

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Submitted on November 5, 2003
Revised on December 6, 2003

Major Quantitative Trait Locus for Resting Heart Rate Maps to a Region on Chromosome 4

Lisa J. Martin^*; Anthony G. Comuzzie; Gabriele E. Sonnenberg; Joel Myklebust; Roland James; Jacqueline Marks; John Blangero; and Ahmed H. Kissebah

From the Department of Pediatrics (L.J.M.), Center for Epidemiology and Biostatistics and the Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Ohio; Department of Genetics (A.G.C., J.B.), Southwest Foundation for Biomedical Research, San Antonio, Tex; Department of Medicine (G.E.S., J.M., R.J., J.M., A.H.K.), TOPS Center for Obesity and Metabolic Research and the Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee.

^* To whom correspondence should be addressed. E-mail: lisa.martin{at}cchmc.org.

Abstract--Multiple studies have identified resting heart rate as a risk factor for cardiovascular disease independent of other cardiovascular disease risk factors (such as dyslipidemia and hypertension). Previous studies have examined heart rate in hypertensive individuals, but little is known about the genetic determination of resting heart rate in a normal population. Therefore, our objective was to perform a genome screen on a population containing normotensive and hypertensive individuals. We performed variance decomposition linkage analysis using maximum likelihood methods at 10 cM intervals in 2209 individuals of predominantly North European ancestry. We estimated the heritability of resting heart rate to be 26% and obtained significant evidence of linkage (logarithm of the odds [LOD]=3.9) for resting heart rate on chromosome 4q. This signal is in the same region as a quantitative trait locus (QTL) for long QT syndrome 4 and a QTL for heart rate in rats. Within the 1-LOD unit support interval, there are 2 strong candidates: ankyrin-B and myozenin 2.

Key words: genetics • pulse • cardiovascular diseases • human

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