Major quantitative trait locus for resting heart rate maps to a region on chromosome 4.
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 approximately 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.
Martin
Lisa J
LJ
Department of Pediatrics, Center for Epidemiology and Biostatistics, Cincinnati Children's Hospital Medical Center, Mail Code 5041, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA. lisa.martin@cchmc.org
Comuzzie
Anthony G
AG
Sonnenberg
Gabriele E
GE
Myklebust
Joel
J
James
Roland
R
Marks
Jacqueline
J
Blangero
John
J
Kissebah
Ahmed H
AH
D000818:Animals; D017487:Ankyrins / Q000235:genetics; D000886:Anthropometry; D002352:Carrier Proteins / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D015331:Cohort Studies; D005060:Europe / Q000208:ethnology; D005260:Female; D006339:Heart Rate / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics; D016013:Likelihood Functions; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics*; D051381:Rats; D012307:Risk Factors; D012737:Sex Factors; D014280:Triglycerides / Q000097:blood; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics
C498994:ANK2 protein, human; C432674:Ank2 protein, rat; D017487:Ankyrins; D002352:Carrier Proteins; C419779:MYOZ2 protein, human; D009124:Muscle Proteins; D014280:Triglycerides