{"doi":"10.17615/mjwt-x036","title":"Genome-wide association study identifies novel loci for type 2 diabetes-Attributed end-stage kidney disease in African Americans","abstract":"Background: End-stage kidney disease (ESKD) is a significant public health concern disproportionately affecting African Americans (AAs). Type 2 diabetes (T2D) is the leading cause of ESKD in the USA, and efforts to uncover genetic susceptibility to diabetic kidney disease (DKD) have had limited success. A prior genome-wide association study (GWAS) in AAs with T2D-ESKD was expanded with additional AA cases and controls and genotypes imputed to the higher density 1000 Genomes reference panel. The discovery analysis included 3432 T2D-ESKD cases and 6977 non-diabetic non-nephropathy controls (N = 10,409), followed by a discrimination analysis in 2756 T2D non-nephropathy controls to exclude T2D-Associated variants. Results: Six independent variants located in or near RND3/RBM43, SLITRK3, ENPP7, GNG7, and APOL1 achieved genome-wide significant association (P < 5 × 10-8) with T2D-ESKD. Following extension analyses in 1910 non-diabetic ESKD cases and 908 non-diabetic non-nephropathy controls, a meta-Analysis of 5342 AA all-cause ESKD cases and 6977 AA non-diabetic non-nephropathy controls revealed an additional novel all-cause ESKD locus at EFNB2 (rs77113398; P = 9.84 × 10-9; OR = 1.94). Exclusion of APOL1 renal-risk genotype carriers identified two additional genome-wide significant T2D-ESKD-Associated loci at GRAMD3 and MGAT4C. A second variant at GNG7 (rs373971520; P = 2.17 × 10-8, OR = 1.46) remained associated with all-cause ESKD in the APOL1-negative analysis. Conclusions: Findings provide further evidence for genetic factors associated with advanced kidney disease in AAs with T2D.","journal":"UNC Libraries","year":2024,"id":499029,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9506,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":803308,"name":"W.S. Post","orcid":null,"position":1,"is_corresponding":false},{"id":24831,"name":"Josyf C. 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Rich","orcid":"0000-0003-3872-7793","position":21,"is_corresponding":false},{"id":591569,"name":"D.W. Bowden","orcid":null,"position":22,"is_corresponding":false},{"id":25007,"name":"Laura J. Rasmussen‐Torvik","orcid":"0000-0002-0820-7300","position":23,"is_corresponding":false},{"id":279178,"name":"Jacob M. Keaton","orcid":"0000-0002-6371-7530","position":24,"is_corresponding":false},{"id":391193,"name":"Rulan S. Parekh","orcid":"0000-0001-6313-5752","position":25,"is_corresponding":false},{"id":459202,"name":"Lijun Ma","orcid":"0000-0002-7763-7793","position":26,"is_corresponding":false},{"id":90098,"name":"Barry I. 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