Systematic comparison of phenome-wide admixture mapping and genome-wide association at biobank-scale
En palabras de los autores
Opportunities remain to leverage population structure in large scale genomic studies for additional insight. Admixture mapping (AM) identifies loci where disease risk differs by ancestral background, offering a complementary strategy to genome-wide association studies (GWAS) in admixed populations. We performed a systematic comparison of AM and GWAS across over 800 clinical phenotypes in Hispanic/Latino (HL) and African American (AA) participants from the BioMe biobank. We developed a well-calibrated AM pipeline tailored to the local ancestry structure of HL (N = 14,876) and AA (N = 8,819). While GWAS identified a greater number of significant associations, AM revealed 77 signals, including 48 not detected by GWAS. AM-tagged variants had 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 emphasizes the importance of applying both GWAS and AM approaches to uncover previously unreported loci in admixed populations. Cullina et al. apply admixture mapping and GWAS at phenome-wide scale in Hispanic/Latino and African American participants, showing that systematic comparison of both methods uncovers complementary disease associations in admixed populations.
Apareció: sábado, 26 de septiembre. Nature Communications. Revista con revisión por pares.