Evidence for a gene influencing heart rate on chromosome 5p13-14 in a meta-analysis of genome-wide scans from the NHLBI Family Blood Pressure Program.
BACKGROUND
Elevated resting heart rate has been shown in multiple studies to be a strong predictor of cardiovascular disease. Previous family studies have shown a significant heritable component to heart rate with several groups conducting genomic linkage scans to identify quantitative trait loci.


METHODS
We performed a genome-wide linkage scan to identify quantitative trait loci influencing resting heart rate among 3,282 Caucasians and 3,989 African-Americans in three independent networks comprising the Family Blood Pressure Program (FBPP) using 368 microsatellite markers. Mean heart rate measurements were used in a regression model including covariates for age, body mass index, pack-years, currently drinking alcohol (yes/no), hypertension status and medication usage to create a standardized residual for each gender/ethnic group within each study network. This residual was used in a nonparametric variance component model to generate a LOD score and a corresponding P value for each ethnic group within each study network. P values from each ethnic group and study network were merged using an adjusted Fisher's combining P values method and the resulting P values were converted to LOD scores. The entire analysis was redone after individuals currently taking beta-blocker medication were removed.


RESULTS
We identified significant evidence of linkage (LOD = 4.62) to chromosome 10 near 142.78 cM in the Caucasian group of HyperGEN. Between race and network groups we identified a LOD score of 1.86 on chromosome 5 (between 39.99 and 45.34 cM) in African-Americans in the GENOA network and the same region produced a LOD score of 1.12 among Caucasians within a different network (HyperGEN). Combining all network and race groups we identified a LOD score of 1.92 (P = 0.0013) on chromosome 5p13-14. We assessed heterogeneity for this locus between networks and ethnic groups and found significant evidence for low heterogeneity (P < or = 0.05).


CONCLUSIONS
We found replication (LOD > 1) between ethnic groups and between study networks with low heterogeneity on chromosome 5p13-14 suggesting that a gene in this region influences resting heart rate.
Laramie
Jason M
JM
Department of Neurology, Boston University School of Medicine, Boston, MA, USA. laramiej@bu.edu
Wilk
Jemma B
JB
Hunt
Steven C
SC
Ellison
R Curtis
RC
Chakravarti
Aravinda
A
Boerwinkle
Eric
E
Myers
Richard H
RH
D000328:Adult; D044383:Black People / Q000235:genetics; D002895:Chromosomes, Human, Pair 5; D005260:Female; D008040:Genetic Linkage; D015894:Genome, Human; D005838:Genotype; D006339:Heart Rate / Q000235:genetics*; D006801:Humans; D008297:Male; D009316:National Institutes of Health (U.S.); D040641:Quantitative Trait Loci; D014481:United States; D044465:White People / Q000235:genetics; D001741:Black or African American