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

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.