The performance of a new local false discovery rate method on tests of association between coronary artery disease (CAD) and genome-wide genetic variants

PLoS One. 2017 Sep 20;12(9):e0185174. doi: 10.1371/journal.pone.0185174. eCollection 2017.

Abstract

The maximum entropy (ME) method is a recently-developed approach for estimating local false discovery rates (LFDR) that incorporates external information allowing assignment of a subset of tests to a category with a different prior probability of following the null hypothesis. Using this ME method, we have reanalyzed the findings from a recent large genome-wide association study of coronary artery disease (CAD), incorporating biologic annotations. Our revised LFDR estimates show many large reductions in LFDR, particularly among the genetic variants belonging to annotation categories that were known to be of particular interest for CAD. However, among SNPs with rare minor allele frequencies, the reductions in LFDR were modest in size.

MeSH terms

  • Coronary Artery Disease / genetics*
  • Gene Frequency*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study / methods*
  • Genome-Wide Association Study / statistics & numerical data
  • Humans
  • Models, Genetic
  • Polymorphism, Single Nucleotide*
  • Probability

Grants and funding

This work was funded primarily by CIHR Operating grant #123508, awarded to DB and CG by the Canadian Institutes of Health Research, and also by an NSERC operating grant to CG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.