Systematic comparison of phenome-wide admixture mapping and genome-wide association in a diverse biobank

Abstract

Biobank-scale association studies that include Hispanic/Latino(a) (HL) and African American (AA) populations remain underrepresented, limiting the discovery of disease associated genetic factors in these groups. We present here a systematic comparison of phenome-wide admixture mapping (AM) and genome-wide association (GWAS) using data from the diverse BioMe biobank in New York City. Our analysis highlights 77 genome-wide significant AM signals, 48 of which were not detected by GWAS, emphasizing the complementary nature of these two approaches. AM-tagged variants show significantly higher minor allele frequency and population differentiation (Fst) while GWAS demonstrated higher odds ratios, underscoring the distinct genetic architecture identified by each method. This study offers a comprehensive phenome-wide AM resource, demonstrating its utility in uncovering novel genetic associations in underrepresented populations, particularly for variants missed by traditional GWAS approaches.