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

Jason M. Laramie, Jemma B. Wilk, Steven Hunt, R. Curtis Ellison, Aravinda Chakravarti, Eric Boerwinkle, Richard H. Myers

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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 betablocker 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 = 0.00 13) on chromosome 5p 13-14. We assessed heterogeneity for this locus between networks and ethnic groups and found significant evidence for low heterogeneity (P ≤ 0.05). Conclusion: We found replication (LOD > 1) between ethnic groups and between study networks with low heterogeneity on chromosome 5p 13-14 suggesting that a gene in this region influences resting heart rate.

Original languageEnglish
Article number17
JournalBMC Medical Genetics
Volume7
DOIs
Publication statusPublished - 1 Mar 2006
Externally publishedYes

Fingerprint

National Heart, Lung, and Blood Institute (U.S.)
Chromosomes, Human, Pair 14
Ethnic Groups
Meta-Analysis
Heart Rate
Genome
Blood Pressure
Chromosomes, Human, Pair 13
Genes
Quantitative Trait Loci
African Americans
Chromosomes, Human, Pair 10
Chromosomes, Human, Pair 5
Alcohol Drinking
Microsatellite Repeats
Body Mass Index
Cardiovascular Diseases
Hypertension

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics(clinical)
  • Genetics

Cite this

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. / Laramie, Jason M.; Wilk, Jemma B.; Hunt, Steven; Ellison, R. Curtis; Chakravarti, Aravinda; Boerwinkle, Eric; Myers, Richard H.

In: BMC Medical Genetics, Vol. 7, 17, 01.03.2006.

Research output: Contribution to journalArticle

Laramie, Jason M. ; Wilk, Jemma B. ; Hunt, Steven ; Ellison, R. Curtis ; Chakravarti, Aravinda ; Boerwinkle, Eric ; Myers, Richard H. / 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. In: BMC Medical Genetics. 2006 ; Vol. 7.
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AU - Chakravarti, Aravinda

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AU - Myers, Richard H.

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