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• W2793967234 abstract "Compared with European Americans, African Americans (AAs) are at higher risk for developing end-stage kidney disease (ESKD). Genome-wide association studies (GWAS) have identified >70 genetic variants associated with kidney function and chronic kidney disease (CKD) in patients with and without diabetes. However, these variants explain a small proportion of disease liability. This study examined the contribution of coding genetic variants for risk of type 2 diabetes (T2D)-attributed ESKD and advanced CKD in AAs.Exome sequencing was performed in 456 AA T2D-ESKD cases, and 936 AA nondiabetic, non-nephropathy control individuals at the discovery stage. A mixed logistic regression model was used for association analysis. Nominal associations (P < 0.05) were replicated in an additional 2020 T2D-ESKD cases and 1121 nondiabetic, non-nephropathy control individuals. A meta-analysis combining 4533 discovery and replication samples was performed. Putative T2D-ESKD associations were tested in additional 1910 nondiabetic ESKD and 219 T2D-ESKD cases, as well as 912 AA nondiabetic non-nephropathy control individuals.A total of 11 suggestive T2D-ESKD associations (P < 1 x 10-4) from 8 loci (PLEKHN1, NADK, RAD51AP2, RREB1, PEX6, GRM8, PRX, APOL1) were apparent in the meta-analysis. Exclusion of APOL1 renal-risk genotype carriers identified 3 additional suggestive loci (OTUD7B, IFITM3, DLGAP5). Rs41302867 in RREB1 displayed consistent association with T2D-ESKD and nondiabetic ESKD (odds ratio: 0.47; P = 1.2 x 10-6 in 4605 all-cause ESKD and 2969 nondiabetic non-nephropathy control individuals).Our findings suggest that coding genetic variants are implicated in predisposition to T2D-ESKD in AAs." @default.
• W2793967234 created "2018-03-29" @default.
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• W2793967234 date "2018-07-01" @default.
• W2793967234 modified "2023-10-13" @default.
• W2793967234 title "An Exome-wide Association Study for Type 2 Diabetes–Attributed End-Stage Kidney Disease in African Americans" @default.
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• W2793967234 doi "https://doi.org/10.1016/j.ekir.2018.03.002" @default.
• W2793967234 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6035163" @default.
• W2793967234 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29989002" @default.
• W2793967234 hasPublicationYear "2018" @default.
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