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 - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Medical Genetics

, 7:17

First Online: 01 March 2006Received: 21 September 2005Accepted: 01 March 2006

Abstract

BackgroundElevated 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.

MethodsWe 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.

ResultsWe 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 ≤ 0.05.

ConclusionWe 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.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2350-7-17 contains supplementary material, which is available to authorized users.

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