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Updated: Jun 10, 2026

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
07:15

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

Published on: January 16, 2019

Gene dosage of the common variant 9p21 predicts severity of coronary artery disease

Sonny Dandona1, Alexandre F R Stewart, Li Chen

  • 1John and Jennifer Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, Canada.

Journal of the American College of Cardiology
|July 31, 2010
PubMed

Insights

Gene dosage of the 9p21 risk variant predicts coronary artery disease severity. Higher gene dosage is linked to more severe disease, including 3-vessel and left main trunk disease.

Area of Science:

  • Cardiovascular Genetics
  • Genomics and Precision Medicine

Background:

  • The 9p21 locus is a significant genetic risk factor for coronary artery disease (CAD) and myocardial infarction.
  • Understanding the role of genetic variants like 9p21 is crucial for personalized risk assessment.

Purpose of the Study:

  • To investigate if 9p21 gene dosage influences the severity of coronary artery disease (CAD).
  • To test the hypothesis that increased 9p21 risk variant copies correlate with more advanced CAD.

Main Methods:

  • A cross-sectional study of 950 early-onset and 764 late-onset CAD patients.
  • Genotyping for the 9p21 single nucleotide polymorphism (SNP) rs1333049.
  • Association analysis of 9p21 gene dosage with CAD extent (3-vessel, 1-vessel, left main trunk disease) and severity scores.

Main Results:

  • 9p21 gene dosage directly correlated with 3-vessel disease and left main trunk disease severity.
  • An inverse association was observed between 9p21 gene dosage and 1-vessel disease.
  • Higher 9p21 gene dosage predicted increased modified Gensini and Duke coronary scores.

Conclusions:

  • The gene dosage of the 9p21 risk variant is a significant predictor of coronary atheromatous burden.
  • This finding supports the role of 9p21 in determining CAD severity, not just risk.
Abstract

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