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Guan M, Keaton JM, Dimitrov L, et al. Genome-wide association study identifies novel loci for type 2 diabetes-attributed end-stage kidney disease in African Americans. Hum Genomics. 2019;13(1):21doi: 10.1186/s40246-019-0205-7.
Guan, M., Keaton, J. M., Dimitrov, L., Hicks, P. J., Xu, J., Palmer, N. D., Ma, L., Das, S. K., Chen, Y. I., Coresh, J., Fornage, M., Franceschini, N., Kramer, H., Langefeld, C. D., Mychaleckyj, J. C., Parekh, R. S., Post, W. S., Rasmussen-Torvik, L. J., Rich, S. S., Rotter, J. I., Sedor, J. R., Thornley-Brown, D., Tin, A., Wilson, J. G., Freedman, B. I., Bowden, D. W., Ng, M. C. Y. (2019). Genome-wide association study identifies novel loci for type 2 diabetes-attributed end-stage kidney disease in African Americans. Human genomics, 13(1), 21. https://doi.org/10.1186/s40246-019-0205-7
Guan, Meijian, et al. "Genome-wide association study identifies novel loci for type 2 diabetes-attributed end-stage kidney disease in African Americans." Human genomics vol. 13,1 (2019): 21. doi: https://doi.org/10.1186/s40246-019-0205-7
Guan M, Keaton JM, Dimitrov L, Hicks PJ, Xu J, Palmer ND, Ma L, Das SK, Chen YI, Coresh J, 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, Ng MCY. Genome-wide association study identifies novel loci for type 2 diabetes-attributed end-stage kidney disease in African Americans. Hum Genomics. 2019 May 15;13(1):21. doi: 10.1186/s40246-019-0205-7. PMID: 31092297; PMCID: PMC6521376.
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Hum Genomics. 2019 May 15;13(1):21. doi: 10.1186/s40246-019-0205-7.

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

Human genomics

Meijian Guan, Jacob M Keaton, Latchezar Dimitrov, Pamela J Hicks, Jianzhao Xu, Nicholette D Palmer, Lijun Ma, Swapan K Das, Yii-Der I Chen, Josef Coresh, Myriam Fornage, Nora Franceschini, Holly Kramer, Carl D Langefeld, Josyf C Mychaleckyj, Rulan S Parekh, Wendy S Post, Laura J Rasmussen-Torvik, Stephen S Rich, Jerome I Rotter, John R Sedor, Denyse Thornley-Brown, Adrienne Tin, James G Wilson, Barry I Freedman, Donald W Bowden, Maggie C Y Ng,

Affiliations

  1. Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  2. Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  3. Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
  4. Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  5. Department of Internal Medicine, Section on Endocrinology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  6. Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
  7. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  8. Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
  9. Department of Epidemiology, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  10. Departments of Public Health Sciences and Medicine, Division of Nephrology and Hypertension, Loyola University Chicago, Maywood, IL, USA.
  11. Department of Medicine, Hines Veteran's Affairs Medical Center, Hines, IL, USA.
  12. Center for Public Health Genomics, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  13. Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  14. Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
  15. Departments of Paediatrics and Medicine, Hospital for Sick Children, University Health Network and the University of Toronto, Toronto, ON, Canada.
  16. Department of Preventive Medicine, Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  17. Division of Genomic Outcomes, Departments of Pediatrics and Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
  18. Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA.
  19. Glickman Urology and Kidney Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
  20. Nephrology, University of Alabama Birmingham, Birmingham, AL, USA.
  21. Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA.
  22. Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA. [email protected].
  23. Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA. [email protected].
  24. Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA. [email protected].

PMID: 31092297 PMCID: PMC6521376 DOI: 10.1186/s40246-019-0205-7

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

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

Keywords: African Americans; Diabetic kidney disease; End-stage kidney disease; Genome-wide association study; Type 2 diabetes

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