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Statistical correction of the Winner’s Curse explains replication variability in quantitative trait genome-wide association studies

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  • Cameron Palmer
  • Itsik Pe’er

Abstract

Genome-wide association studies (GWAS) have identified hundreds of SNPs responsible for variation in human quantitative traits. However, genome-wide-significant associations often fail to replicate across independent cohorts, in apparent inconsistency with their apparent strong effects in discovery cohorts. This limited success of replication raises pervasive questions about the utility of the GWAS field. We identify all 332 studies of quantitative traits from the NHGRI-EBI GWAS Database with attempted replication. We find that the majority of studies provide insufficient data to evaluate replication rates. The remaining papers replicate significantly worse than expected (p

Suggested Citation

  • Cameron Palmer & Itsik Pe’er, 2017. "Statistical correction of the Winner’s Curse explains replication variability in quantitative trait genome-wide association studies," PLOS Genetics, Public Library of Science, vol. 13(7), pages 1-18, July.
    • Handle: RePEc:plo:pgen00:1006916
    DOI: 10.1371/journal.pgen.1006916
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    Cited by:

    1. Zichen Zhang & Ye Eun Bae & Jonathan R. Bradley & Lang Wu & Chong Wu, 2022. "SUMMIT: An integrative approach for better transcriptomic data imputation improves causal gene identification," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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