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Genome-wide association study identifies novel loci for type 2 diabetes-attributed end-stage kidney disease in African Americans.

TitleGenome-wide association study identifies novel loci for type 2 diabetes-attributed end-stage kidney disease in African Americans.
Publication TypeJournal Article
Year of Publication2019
AuthorsGuan M, Keaton JM, Dimitrov L, Hicks PJ, Xu J, Palmer ND, Ma L, Das SK, Chen Y-DI, Coresh JJ, Fornage M, Franceschini N, Kramer H, Langefeld CD, Mychaleckyj JC, Parekh RS, Post WS, Rasmussen-Torvik LJ, Rich SS, Rotter JI, Sedor JR, Thornley-Brown D, Tin A, Wilson JG, Freedman BI, Bowden DW
Secondary AuthorsC Y Ng M
Corporate AuthorsFIND Consortium
JournalHum Genomics
Volume13
Issue1
Pagination21
Date Published2019 05 15
ISSN1479-7364
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 

CONCLUSIONS: Findings provide further evidence for genetic factors associated with advanced kidney disease in AAs with T2D.

DOI10.1186/s40246-019-0205-7
Alternate JournalHum Genomics
PubMed ID31092297
PubMed Central IDPMC6521376
Grant ListHHSN268201300026C / HL / NHLBI NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
U01 DK057300 / DK / NIDDK NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
R01 DK117445 / DK / NIDDK NIH HHS / United States
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HHSC268200782096C, DK081350, DK066358, DK053591, DK087914, DK105556, HL56266, DK070941 / NH / NIH HHS / United States
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HHSN268201700003I / HL / NHLBI NIH HHS / United States
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M01 RR07122 / / Wake Forest School of Medicine / International
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HHSN268201300049C, HHSN268201300050C, HHSN268201300048C, HHSN268201300046C, HHSN268201300047C / NH / NIH HHS / United States
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HHSN268201300029C / HL / NHLBI NIH HHS / United States
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