Genome-wide association of albuminuria and chronic kidney disease in American Indians and Hispanics/Latinos

Background American Indians and Hispanics/Latinos have a high burden of chronic kidney disease (CKD) and they may share disease associated genetic variants. This study aims to identify loci for CKD and albuminuria that are shared between these populations. Methods We performed genome-wide association studies (GWAS) in 3157 American Indians and 12 625 Hispanics/Latinos for CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2) and albuminuria (urine albumin to creatinine ratio [uACR]) > 30 mg/g). We examined significant associations across GWASs and the functional relevance of findings. Results Five low-frequency variants at chromosome 7 were significantly associated with albuminuria in American Indians (lead variant: rs4370473, intronic to KCND2, P = 8.93 × 10−9), with evidence for a partly independent association driven by rs7791185 (p conditional on rs4370473 = 3.8 × 10−5). A chromosome 11 variant (rs59232451, HBE1-HBB locus, P = 4.9 × 10−8) was significantly associated with albuminuria in Hispanics/Latinos when adjusting for diabetes, and the association was partially accounted for by the HBB rs344. The associations for albuminuria did not cross-replicate among studies. There were no significant associations with CKD. Conclusions Our study identified associations at KCND2 in American Indians and HBE1-HBB in Hispanics/Latinos for albuminuria. Findings suggest differences in genetic architecture influencing albuminuria across these populations.