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

Autor: Guan M; Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.; Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA., Keaton JM; Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.; Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA., Dimitrov L; Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.; Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA., Hicks PJ; Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.; Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA., Xu J; Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.; Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA., Palmer ND; Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.; Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA., Ma L; Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC, USA., Das SK; Department of Internal Medicine, Section on Endocrinology, Wake Forest School of Medicine, Winston-Salem, NC, USA., Chen YI; Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA., Coresh J; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Fornage M; Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA., Franceschini N; Department of Epidemiology, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Kramer H; Departments of Public Health Sciences and Medicine, Division of Nephrology and Hypertension, Loyola University Chicago, Maywood, IL, USA.; Department of Medicine, Hines Veteran's Affairs Medical Center, Hines, IL, USA., Langefeld CD; Center for Public Health Genomics, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.; Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA., Mychaleckyj JC; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA., Parekh RS; Departments of Paediatrics and Medicine, Hospital for Sick Children, University Health Network and the University of Toronto, Toronto, ON, Canada., Post WS; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Rasmussen-Torvik LJ; Department of Preventive Medicine, Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Rich SS; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA., Rotter JI; Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.; Division of Genomic Outcomes, Departments of Pediatrics and Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA., Sedor JR; Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA.; Glickman Urology and Kidney Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Thornley-Brown D; Nephrology, University of Alabama Birmingham, Birmingham, AL, USA., Tin A; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Wilson JG; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA., Freedman BI; Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC, USA., Bowden DW; Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.; Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA., Ng MCY; Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA. maggie.ng@vumc.org.; Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA. maggie.ng@vumc.org.; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA. maggie.ng@vumc.org.
Jazyk: angličtina
Zdroj: Human genomics [Hum Genomics] 2019 May 15; Vol. 13 (1), pp. 21. Date of Electronic Publication: 2019 May 15.
DOI: 10.1186/s40246-019-0205-7
Abstrakt: 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.
Databáze: MEDLINE
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