Large-scale admixture mapping in the All of Us Research Program improves the characterization of cross-population phenotypic differences

Admixed individuals have been understudied in medical research largely due to their complex genetic ancestries. However, the consideration of admixture can identify ancestry-enriched genetic associations, delineating some of the genetic underpinnings of cross-population phenotypic variation. Here, we performed admixture mapping in individuals with inferred admixture from African and European populations (N=48,921). Across 22 traits, we identified 71 ancestry-trait associations, highlighting loci where ancestral haplotypes explained some phenotypic variation yet single-variant association analyses missed due to their stricter multiple testing burden. One such locus where inferred local AFR ancestries associated with increased hemoglobin A1c (HbA1c) was 12q14.3, highlighting its potential role in HbA1c differences between populations. Together, our results expand upon the phenotypic differences between populations, highlighting loci where genetic ancestries play a critical role in the genetic architecture of disease.