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J Hum Genet. 2016 Oct;61(10):861-866. doi: 10.1038/jhg.2016.72. Epub 2016 Jun 16.

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

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Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Bioresource Research Center, Tokyo Medical and Dental University, Tokyo, Japan.
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan.


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.

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