Empirical estimation of genome-wide significance thresholds based on the 1000 Genomes Project data set

To assess the statistical significance of associations between variants and traits, genome-wide association studies (gwas) should employ an appropriate threshold that accounts for the massive burden of multiple testing in the study. although most studies in the current literature commonly set a genome-wide significance threshold at the level of p=5.0 × 10−8, the adequacy of this value for respective populations has not been fully investigated. to empirically estimate thresholds for different ancestral populations, we conducted gwas simulations using the 1000 genomes phase 3 data set for africans (afr), europeans (eur), admixed americans (amr), east asians (eas) and south asians (sas). the estimated empirical genome-wide significance thresholds were psig=3.24 × 10−8 (afr), 9.26 × 10−8 (eur), 1.83 × 10−7 (amr), 1.61 × 10−7 (eas) and 9.46 × 10−8 (sas). we additionally conducted trans-ethnic meta-analyses across all populations (all) and all populations except for afr (δafr), which yielded psig=3.25 × 10−8 (all) and 4.20 × 10−8 (δafr). our results indicate that the current threshold (p=5.0 × 10−8) is overly stringent for all ancestral populations except for africans; however, we should employ a more stringent threshold when conducting a meta-analysis, regardless of the presence of african samples.