Genome-wide significance is widely defined as a statistical association between a genetic variant and a trait in which the p-value ≤ 5e-8 in a genome-wide association study (GWAS).
As with all p-value thresholds for "statistical significance", the value is arbitrary. The threshold of p ≤ 5e-8 was a Bonferroni correction of the commonly used p ≤ 0.05, based on the estimated number of independent tests in the GWAS if all common single nucleotide polymorphisms (SNPs) in the first version of HapMap were tested with direct genotyping or imputation. More stringent thresholds should be used if the study also included rare variants or whole-genome sequencing was used. The major feature of a reliable genetic association, however, is replication in an independent sample.
References
- Panagiotou OA, Ioannidis JP. Genome-Wide Significance P. What should the genome-wide significance threshold be? Empirical replication of borderline genetic associations. Int J Epidemiol 2012; 41: 273-86.
- Sterne JAC, Davey Smith G. Shifting the evidence - what's wrong with significance tests? BMJ (Clinical research ed) 2001; 322: 226-231.