P < 5 × 10-8 has emerged as a standard of statistical significance for genome-wide association studies

Anne Sophie Jannot, Georg Ehret, Thomas Perneger

Research output: Contribution to journalArticle

Abstract

Abstract Objectives In genome-wide association studies (GWASs), the practice regarding the choice of thresholds of significance and of thresholds used to include single nucleotide polymorphisms (SNPs) in a further validation stage is not well known. Here, we performed a systematic analysis of all GWASs published in two recent but nonconsecutive periods to assess whether any consensus was emerging regarding the choice of these thresholds. Study Design and Setting We identified 167 GWASs published during the first semester of 2011 and 105 published in the third trimester of 2012 and retrieved the genome-wide threshold of significance and the thresholds to include SNPs in a replication stage if applicable. Results The proportion of studies using 5 × 10-8 as a genome-wide significance threshold increased between 2011 and 2012 (40% vs. 64%, P < 0.001), whereas the proportion of articles that gave a justification for this threshold decreased. The distribution of thresholds used to include SNPs in the replication stage remained stable over time (median 10-5), and the variance remained large [interquartile range (10-6, 10-4)]. Conclusion Although 5 × 10-8 has become the de facto standard genome-wide threshold, practice regarding the choice of inclusion threshold for the replication step remains heterogeneous and did not ensure the best trade-off between power and type 1 error.

Original languageEnglish (US)
Article number8783
Pages (from-to)460-465
Number of pages6
JournalJournal of Clinical Epidemiology
Volume68
Issue number4
DOIs
StatePublished - Apr 1 2015

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Keywords

  • Evaluation studies as topic
  • False discovery rate
  • Genome-wide association study
  • Multiple testing
  • Significance thresholds
  • Validation studies

ASJC Scopus subject areas

  • Epidemiology

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