Mixed mapping of Estimated Glomerular Filtration Rate is a strong strategy for gene mapping of complex phenotypes that takes advantage of the broad genetic background of recent admixture populations, such as Hispanic or Latino persons in the United States. These people are at a higher risk of developing CKD. For a study, researchers performed genome-wide admixture mapping for both CKD and eGFR in a sample of 12,601 Hispanic Community Health Study/Study of Latinos individuals, with validation in a sample of 8,191 Black Women’s Health Initiative (WHI) participants. They also compared the results to those of a traditional genome-wide association analysis.
Three new ancestry-of-origin loci for CKD and eGFR were discovered on chromosomes 2, 14, and 15. The chromosome 2 locus has two ancestry areas that include the FSHR and NRXN1 genes, with ancestry at this locus linked with an elevated risk of CKD. The chromosome 14 locus, which was discovered inside the DLK1-DIO3 imprinted region, was linked to decreased eGFR and was influenced by European ancestry. The eGFR-associated locus on chromosome 15 included intronic RYR3 mutations and was located in an African-specific genomic area linked to greater eGFR. The genome-wide association analysis was unable to find any meaningful relationships in these areas. In WHI Black subjects, they verified the chromosome 14 & 15 loci linked to eGFR.
The work demonstrated the possibility for harnessing genetic heritage in recently admixed populations to find novel candidate loci for kidney phenotypes by demonstrating the influence of shared ancestry-specific genomic areas on eGFR in Hispanic or Latino persons and Black individuals.