Linkage disequilibrium and haplotype diversity in the genes of the renin-angiotensin system: Findings from the family blood pressure program

Xiaofeng Zhu, Denise Yan, Richard S. Cooper, Amy Luke, Morna A. Ikeda, Yen Pei C Chang, Alan Weder, Aravinda Chakravarti

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Association studies of candidate genes with complex traits have generally used one or a few single nucleotide polymorphisms (SNPs), although variation in the extent of linkage disequilibrium (LD) within genes markedly influences the sensitivity and precision of association studies. The extent of LD and the underlying haplotype structure for most candidate genes are still unavailable. We sampled 193 blacks (African-Americans) and 160 whites (European-Americans) and estimated the intragenic LD and the haplotype structure in four genes of the renin-angiotensin system. We genotyped 25 SNPs, with all but one of the pairs spaced between 1 and 20 kb, thus providing resolution at small scale. The pattern of LD within a gene was very heterogeneous. Using a robust method to define haplotype blocks, blocks of limited haplotype diversity were identified at each locus; between these blocks, LD was lost owing to the history of recombination events. As anticipated, there was less LD among blacks, the number of haplotypes was substantially larger, and shorter haplotype segments were found, compared with whites. These findings have implications for candidate-gene association studies and indicate that variation between populations of European and African origin in haplotype diversity is characteristic of most genes.

Original languageEnglish
Pages (from-to)173-181
Number of pages9
JournalGenome Research
Volume13
Issue number2
DOIs
StatePublished - Feb 1 2003
Externally publishedYes

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Linkage Disequilibrium
Renin-Angiotensin System
Haplotypes
Blood Pressure
Genes
Genetic Association Studies
Single Nucleotide Polymorphism
African Americans
Genetic Recombination
History
Population

ASJC Scopus subject areas

  • Genetics

Cite this

Linkage disequilibrium and haplotype diversity in the genes of the renin-angiotensin system : Findings from the family blood pressure program. / Zhu, Xiaofeng; Yan, Denise; Cooper, Richard S.; Luke, Amy; Ikeda, Morna A.; Chang, Yen Pei C; Weder, Alan; Chakravarti, Aravinda.

In: Genome Research, Vol. 13, No. 2, 01.02.2003, p. 173-181.

Research output: Contribution to journalArticle

Zhu, Xiaofeng ; Yan, Denise ; Cooper, Richard S. ; Luke, Amy ; Ikeda, Morna A. ; Chang, Yen Pei C ; Weder, Alan ; Chakravarti, Aravinda. / Linkage disequilibrium and haplotype diversity in the genes of the renin-angiotensin system : Findings from the family blood pressure program. In: Genome Research. 2003 ; Vol. 13, No. 2. pp. 173-181.
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