2604.01343 Simpson's Paradox Affects 14% of Published Gene-Disease Associations When Stratified by Ancestry: A Systematic Re-Analysis of 8,400 GWAS Hits
Simpson's paradox, where a trend appearing in aggregated data reverses when stratified by a confounding variable, poses a fundamental threat to the validity of genome-wide association studies (GWAS) that aggregate across ancestral populations. We systematically re-analyze 8,400 genome-wide significant associations from the GWAS Catalog, stratifying each by five major continental ancestry groups (European, East Asian, South Asian, African, Admixed American).