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Jannot AS, Ehret G, Perneger T. P < 5 × 10(-8) has emerged as a standard of statistical significance for genome-wide association studies. J Clin Epidemiol. 2015;68(4):460-5doi: 10.1016/j.jclinepi.2015.01.001.
Jannot, A. S., Ehret, G., & Perneger, T. (2015). P < 5 × 10(-8) has emerged as a standard of statistical significance for genome-wide association studies. Journal of clinical epidemiology, 68(4), 460-5. https://doi.org/10.1016/j.jclinepi.2015.01.001
Jannot, Anne-Sophie, et al. "P < 5 × 10(-8) has emerged as a standard of statistical significance for genome-wide association studies." Journal of clinical epidemiology vol. 68,4 (2015): 460-5. doi: https://doi.org/10.1016/j.jclinepi.2015.01.001
Jannot AS, Ehret G, Perneger T. P < 5 × 10(-8) has emerged as a standard of statistical significance for genome-wide association studies. J Clin Epidemiol. 2015 Apr;68(4):460-5. doi: 10.1016/j.jclinepi.2015.01.001. Epub 2015 Jan 09. PMID: 25666886.
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J Clin Epidemiol. 2015 Apr;68(4):460-5. doi: 10.1016/j.jclinepi.2015.01.001. Epub 2015 Jan 09.

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

Journal of clinical epidemiology

Anne-Sophie Jannot, Georg Ehret, Thomas Perneger

Affiliations

  1. Division of Clinical Epidemiology, University Hospitals of Geneva, rue Gabrielle Perret-Gentil 4, 1211 Geneva, Switzerland. Electronic address: [email protected].
  2. Division of Cardiology, University Hospitals of Geneva, rue Gabrielle Perret-Gentil 4, 1211 Geneva, Switzerland.
  3. Division of Clinical Epidemiology, University Hospitals of Geneva, rue Gabrielle Perret-Gentil 4, 1211 Geneva, Switzerland.

PMID: 25666886 DOI: 10.1016/j.jclinepi.2015.01.001

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.

Copyright © 2015 Elsevier Inc. All rights reserved.

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

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