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A Powerful Procedure for Pathway-Based Meta-analysis Using Summary Statistics Identifies 43 Pathways Associated with Type II Diabetes in European Populations

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  • Han Zhang
  • William Wheeler
  • Paula L Hyland
  • Yifan Yang
  • Jianxin Shi
  • Nilanjan Chatterjee
  • Kai Yu

Abstract

Meta-analysis of multiple genome-wide association studies (GWAS) has become an effective approach for detecting single nucleotide polymorphism (SNP) associations with complex traits. However, it is difficult to integrate the readily accessible SNP-level summary statistics from a meta-analysis into more powerful multi-marker testing procedures, which generally require individual-level genetic data. We developed a general procedure called Summary based Adaptive Rank Truncated Product (sARTP) for conducting gene and pathway meta-analysis that uses only SNP-level summary statistics in combination with genotype correlation estimated from a panel of individual-level genetic data. We demonstrated the validity and power advantage of sARTP through empirical and simulated data. We conducted a comprehensive pathway-based meta-analysis with sARTP on type 2 diabetes (T2D) by integrating SNP-level summary statistics from two large studies consisting of 19,809 T2D cases and 111,181 controls with European ancestry. Among 4,713 candidate pathways from which genes in neighborhoods of 170 GWAS established T2D loci were excluded, we detected 43 T2D globally significant pathways (with Bonferroni corrected p-values

Suggested Citation

  • Han Zhang & William Wheeler & Paula L Hyland & Yifan Yang & Jianxin Shi & Nilanjan Chatterjee & Kai Yu, 2016. "A Powerful Procedure for Pathway-Based Meta-analysis Using Summary Statistics Identifies 43 Pathways Associated with Type II Diabetes in European Populations," PLOS Genetics, Public Library of Science, vol. 12(6), pages 1-28, June.
    • Handle: RePEc:plo:pgen00:1006122
    DOI: 10.1371/journal.pgen.1006122
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    References listed on IDEAS

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    1. Marina Evangelou & Augusto Rendon & Willem H Ouwehand & Lorenz Wernisch & Frank Dudbridge, 2012. "Comparison of Methods for Competitive Tests of Pathway Analysis," PLOS ONE, Public Library of Science, vol. 7(7), pages 1-10, July.
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    1. Derek W. Brown & Liam D. Cato & Yajie Zhao & Satish K. Nandakumar & Erik L. Bao & Eugene J. Gardner & Aubrey K. Hubbard & Alexander DePaulis & Thomas Rehling & Lei Song & Kai Yu & Stephen J. Chanock &, 2023. "Shared and distinct genetic etiologies for different types of clonal hematopoiesis," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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