Frontiers in Cardiovascular Medicine (Sep 2017)

Genome-Wide Association Analysis for Severity of Coronary Artery Disease Using the Gensini Scoring System

  • Tanja Zeller,
  • Tanja Zeller,
  • Moritz Seiffert,
  • Moritz Seiffert,
  • Christian Müller,
  • Christian Müller,
  • Markus Scholz,
  • Markus Scholz,
  • Anna Schäffer,
  • Francisco Ojeda,
  • Heinz Drexel,
  • Heinz Drexel,
  • Heinz Drexel,
  • Axel Mündlein,
  • Marcus E. Kleber,
  • Winfried März,
  • Winfried März,
  • Winfried März,
  • Christoph Sinning,
  • Fabian J. Brunner,
  • Christoph Waldeyer,
  • Till Keller,
  • Till Keller,
  • Christoph H. Saely,
  • Christoph H. Saely,
  • Christoph H. Saely,
  • Karsten Sydow,
  • Joachim Thiery,
  • Joachim Thiery,
  • Daniel Teupser,
  • Daniel Teupser,
  • Stefan Blankenberg,
  • Stefan Blankenberg,
  • Renate Schnabel,
  • Renate Schnabel

DOI
https://doi.org/10.3389/fcvm.2017.00057
Journal volume & issue
Vol. 4

Abstract

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Coronary artery disease (CAD) has a complex etiology involving numerous environmental and genetic factors of disease risk. To date, the genetic 9p21 locus represents the most robust genetic finding for prevalent and incident CAD. However, limited information is available on the genetic background of the severity and distribution of CAD. CAD manifests itself as stable CAD or acute coronary syndrome. The Gensini score quantifies the extent CAD but requires coronary angiography. Here, we aimed to identify novel genetic variants associated with Gensini score severity and distribution of CAD. A two-stage approach including a discovery and a replication stage was used to assess genetic variants. In the discovery phase, a meta-analysis of genome-wide association data of 4,930 CAD-subjects assessed by the Gensini score was performed. Selected single nucleotide polymorphisms (SNPs) were replicated in 2,283 CAD-subjects by de novo genotyping. We identified genetic loci located on chromosome 2 and 9 to be associated with Gensini score severity and distribution of CAD in the discovery stage. Although the loci on chromosome 2 could not be replicated in the second stage, the known CAD-locus on chromosome 9p21, represented by rs133349, was identified and, thus, was confirmed as risk locus for CAD severity.

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