Using gene expression to improve the power of genome-wide association analysis

Hum Hered. 2014;78(2):94-103. doi: 10.1159/000362837. Epub 2014 Jul 30.

Abstract

Background/aims: Genome-wide association (GWA) studies have reported susceptible regions in the human genome for many common diseases and traits; however, these loci only explain a minority of trait heritability. To boost the power of a GWA study, substantial research endeavors have been focused on integrating other available genomic information in the analysis. Advances in high through-put technologies have generated a wealth of genomic data and made combining SNP and gene expression data become feasible.

Results: In this paper, we propose a novel procedure to incorporate gene expression information into GWA analysis. This procedure utilizes weights constructed by gene expression measurements to adjust p values from a GWA analysis. RESULTS from simulation analyses indicate that the proposed procedures may achieve substantial power gains, while controlling family-wise type I error rates at the nominal level. To demonstrate the implementation of our proposed approach, we apply the weight adjustment procedure to a GWA study on serum interferon-regulated chemokine levels in systemic lupus erythematosus patients. The study results can provide valuable insights for the functional interpretation of GWA signals.

Availability: The R source code for implementing the proposed weighting procedure is available at http://www.biostat.umn.edu/∼yho/research.html.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biomarkers / blood
  • Chemokine CCL19 / blood
  • Chemokine CCL2 / blood
  • Chemokine CXCL10 / blood
  • Computer Simulation
  • Female
  • Gene Expression*
  • Genome, Human
  • Genome-Wide Association Study*
  • Humans
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / genetics*
  • Male
  • Polymorphism, Single Nucleotide
  • Whites / genetics

Substances

  • Biomarkers
  • CCL19 protein, human
  • CCL2 protein, human
  • CXCL10 protein, human
  • Chemokine CCL19
  • Chemokine CCL2
  • Chemokine CXCL10