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Genome-wide linkage scan identifies two novel genetic loci for coronary artery disease: in GeneQuest families

Academic Article
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Overview

authors

  • Gao, H.
  • Li, L.
  • Rao, S.
  • Shen, G.
  • Xi, Q.
  • Chen, S.
  • Zhang, Z.
  • Wang, K.
  • Ellis, S. G.
  • Chen, Q.
  • Topol, Eric
  • Wang, Q. K.

publication date

  • 2014

journal

  • PLoS One  Journal

abstract

  • Coronary artery disease (CAD) is the leading cause of death worldwide. Recent genome-wide association studies (GWAS) identified >50 common variants associated with CAD or its complication myocardial infarction (MI), but collectively they account for <20% of heritability, generating a phenomena of "missing heritability". Rare variants with large effects may account for a large portion of missing heritability. Genome-wide linkage studies of large families and follow-up fine mapping and deep sequencing are particularly effective in identifying rare variants with large effects. Here we show results from a genome-wide linkage scan for CAD in multiplex GeneQuest families with early onset CAD and MI. Whole genome genotyping was carried out with 408 markers that span the human genome by every 10 cM and linkage analyses were performed using the affected relative pair analysis implemented in GENEHUNTER. Affected only nonparametric linkage (NPL) analysis identified two novel CAD loci with highly significant evidence of linkage on chromosome 3p25.1 (peak NPL  = 5.49) and 3q29 (NPL  = 6.84). We also identified four loci with suggestive linkage on 9q22.33, 9q34.11, 17p12, and 21q22.3 (NPL  = 3.18-4.07). These results identify novel loci for CAD and provide a framework for fine mapping and deep sequencing to identify new susceptibility genes and novel variants associated with risk of CAD.

subject areas

  • Adult
  • Age of Onset
  • Chromosome Mapping
  • Coronary Artery Disease
  • Family
  • Female
  • Genetic Association Studies
  • Genetic Linkage
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Male
  • Middle Aged
  • Population Surveillance
  • United States
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Identity

PubMed Central ID

  • PMC4259362

International Standard Serial Number (ISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0113935

PubMed ID

  • 25485937
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Additional Document Info

start page

  • e113935

volume

  • 9

issue

  • 12

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