Admixture Mapping of Diabetic Nephropathy Genetic Variants
Authors: Melendez Ashley Jayanne , Martinez Juan Carlos , Winkler Cheryl 
Published: June 2021

The goal of our research study is to identify diabetes dependent genetic variants that confer susceptibility or resistance to the development of kidney disease. It is thought, based on previous studies, that the susceptibility is associated with African ancestry. We therefore hypothesized that the risk variants might be enriched on African‐derived chromosomal segments in cases. A genome‐wide, agnostic method to search for susceptibility variants that are more common in one ancestral group than others is to compare ancestry of chromosomal segments in admixed populations. By identifying these African‐derived enriched chromosomal regions in cases compared to controls or to the rest of the genome in a case‐only study, we can localize risk variants. Puerto Ricans are thought to have 3‐way ethnicity admixture (Indigenous, European, and African). In view of this wide admixture, researching in a population like Puerto Rico allows a broader study of variants and their ancestral origin. The underlying goal is to identify chromosomal regions associated with disease phenotype, followed by fine‐mapping to identify the causal gene. The human subjects in this study are End‐Stage Kidney Disease (ESKD) patients from the West side of Puerto Rico. We anticipate enrolling over 1,000 patients from dialysis centers. DNA from the saliva samples from the ESKD patients will be genotyped for over 10,000 Single Nucleotide Polymorphisms (SNP) using Illumina Technology at the National Cancer Institute in Frederick, Maryland. Among these SNPs there is Ancestry Informative Markers (AIM) that will be analyzed using Mapping by Admixture Linkage Disequilibrium (MALD) technique as an approach. This technique is used to determine the extent of African, European, and Native American ancestry across the 23 chromosomes. Chromosomal regions showing significantly increased or decreased ancestry will be considered candidate regions for harboring susceptibility or resistant genes. We will also use a candidate approach and genotype known genes found to associate with kidney disease, including single nucleotide polymorphisms rs60910145, rs71785313 (allele variant G1) and rs73885319 (allele variant G2) from the APOL1 gene (apolipoprotein L1). The APOL1 gene variant is found only on African‐derived chromosomes, and was associated with kidney disease on previous studies. This research should result in the discovery of new variants associated with diabetic nephropathy. Approximately 300 have already volunteered. All 300 samples were already genotyped for all SNPs of the APOL1 gene. Analysis on the data retrieved reveals a relationship with diabetic nephropathy and all three variants. Once other diabetic nephropathy associated variants are determined, we expect them to have an increase in African ancestry, as well to observe the relationship already established with the APOL1 gene.

Support or Funding Information

This research was supported by the National Institute Of General Medical Sciences of the National Institutes of Health under Award Number T34GM008419 and by an Institutional developmental Award (IDeA) from the National Institute Of General Medical Sciences of the National Institutes of Health under grant number P20 GM103475‐15.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.