Five blood pressure loci identified by an updated genome-wide linkage scan: Meta-analysis of the family blood pressure program

Jeannette Simino, Gang Shi, Rezart Kume, Karen Schwander, Michael A. Province, C. Charles Gu, Sharon Kardia, Aravinda Chakravarti, Georg Ehret, Richard A. Olshen, Stephen T. Turner, Low Tone Ho, Xiaofeng Zhu, Cashell Jaquish, Dina Paltoo, Richard S. Cooper, Alan Weder, J. David Curb, Eric Boerwinkle, Steven C. HuntDabeeru C. Rao

Research output: Contribution to journalArticle

Abstract

Background A preliminary genome-wide linkage analysis of blood pressure in the Family Blood Pressure Program (FBPP) was reported previously. We harnessed the power and ethnic diversity of the final pooled FBPP dataset to identify novel loci for blood pressure thereby enhancing localization of genes containing less common variants with large effects on blood pressure levels and hypertension.MethodsWe performed one overall and 4 race-specific meta-analyses of genome-wide blood pressure linkage scans using data on 4,226 African-American, 2,154 Asian, 4,229 Caucasian, and 2,435 Mexican-American participants (total N = 13,044). Variance components models were fit to measured (raw) blood pressure levels and two types of antihypertensive medication adjusted blood pressure phenotypes within each of 10 subgroups defined by race and network. A modified Fisher's method was used to combine the P values for each linkage marker across the 10 subgroups.ResultsFive quantitative trait loci (QTLs) were detected on chromosomes 6p22.3, 8q23.1, 20q13.12, 21q21.1, and 21q21.3 based on significant linkage evidence (defined by logarithm of odds (lod) score 3) in at least one meta-analysis and lod scores 1 in at least 2 subgroups defined by network and race. The chromosome 8q23.1 locus was supported by Asian-, Caucasian-, and Mexican-American-specific meta-analyses. ConclusionsThe new QTLs reported justify new candidate gene studies. They may help support results from genome-wide association studies (GWAS) that fall in these QTL regions but fail to achieve the genome-wide significance.

Original languageEnglish (US)
Pages (from-to)347-354
Number of pages8
JournalAmerican Journal of Hypertension
Volume24
Issue number3
DOIs
StatePublished - Mar 2011

Keywords

  • QTL
  • blood pressure
  • genetics
  • hypertension
  • linkage
  • meta-analysis

ASJC Scopus subject areas

  • Internal Medicine

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    Simino, J., Shi, G., Kume, R., Schwander, K., Province, M. A., Gu, C. C., Kardia, S., Chakravarti, A., Ehret, G., Olshen, R. A., Turner, S. T., Ho, L. T., Zhu, X., Jaquish, C., Paltoo, D., Cooper, R. S., Weder, A., Curb, J. D., Boerwinkle, E., ... Rao, D. C. (2011). Five blood pressure loci identified by an updated genome-wide linkage scan: Meta-analysis of the family blood pressure program. American Journal of Hypertension, 24(3), 347-354. https://doi.org/10.1038/ajh.2010.238