Post-GWAS Prioritization Through Data Integration Provides Novel Insights on Chronic Obstructive Pulmonary Disease

  • Qiongshi Lu
  • Chentian Jin
  • Jiehuan Sun
  • Russell Bowler
  • Katerina Kechris
  • Naftali Kaminski
  • Hongyu Zhao
Article

Abstract

Rich collections of genomic and epigenomic annotations, availabilities of large population cohorts for genome-wide association studies (GWASs), and advancements in data integration techniques provide the unprecedented opportunity to accelerate discoveries in complex disease studies through integrative analyses. In this paper, we apply a variety of approaches to integrate GWAS summary statistics of chronic obstructive pulmonary disease (COPD) with functional annotations to illustrate how data integration could help researchers understand complex human diseases. We show that incorporating functional annotations can better prioritize GWAS signals at both the global and the local levels. Signal prioritization on severe COPD GWAS reveals multiple potential risk loci that are linked with pulmonary functions. Enrichment analysis provides novel insights on the pathogenesis of COPD and hints the existence of genetic contributions to muscle dysfunction and chronic lung inflammation, two symptoms that are often comorbid with COPD. Our results suggest that rich signals for COPD genetics are still buried under the Bonferroni-corrected genome-wide significance threshold. Many more biological findings are expected to emerge as more samples are recruited for COPD studies.

Keywords

Chronic obstructive pulmonary disease Data integration GWAS Functional annotation 

Supplementary material

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Supplementary material 1 (doc 1408 KB)

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Copyright information

© International Chinese Statistical Association 2016

Authors and Affiliations

  • Qiongshi Lu
    • 1
  • Chentian Jin
    • 2
  • Jiehuan Sun
    • 1
  • Russell Bowler
    • 3
  • Katerina Kechris
    • 4
  • Naftali Kaminski
    • 5
  • Hongyu Zhao
    • 1
    • 6
    • 7
  1. 1.Department of BiostatisticsYale School of Public HealthNew HavenUSA
  2. 2.Yale CollegeNew HavenUSA
  3. 3.Department of MedicineNational Jewish HealthDenverUSA
  4. 4.Department of Biostatistics and InformaticsUniversity of Colorado DenverDenverUSA
  5. 5.Pulmonary, Critical Care and Sleep MedicineYale School of MedicineNew HavenUSA
  6. 6.Program of Computational Biology and BioinformaticsYale UniversityNew HavenUSA
  7. 7.VA Cooperative Studies Program Coordinating CenterWest HavenUSA

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