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

  1. Author:
    Guan, Meijian
    Keaton, Jacob M.
    Dimitrov, Latchezar
    Hicks, Pamela J.
    Xu, Jianzhao
    Palmer, Nicholette D.
    Ma, Lijun
    Das, Swapan K.
    Chen, Yii-Der
    Coresh, Josef
    Fornage, Myriam
    Franceschini, Nora
    Kramer, Holly
    Langefeld, Carl D.
    Mychaleckyj, Josyf C.
    Parekh, Rulan S.
    Post, Wendy S.
    Rasmussen-Torvik, Laura J.
    Rich, Stephen S.
    Rotter, Jerome
    Sedor, John R.
    Thornley-Brown, Denyse
    Tin, Adrienne
    Wilson, James G.
    Freedman, Barry
    Bowden, Donald W.
    Ng, Maggie C. Y.
    Iyengar, S. K.
    Elston, R. C.
    Goddard, K. A. B.
    Olson, J. M.
    Ialacci, S.
    Fondran, J.
    Horvath, A.
    Igo, R.
    Jun, G.
    Kramp, K.
    Molineros, J.
    Quade, S. R. E.
    Sedor, J. R.
    Schelling, J.
    Pickens, A.
    Humbert, L.
    Getz-Fradley, L.
    Adler, S.
    Ipp, E.
    Pahl, M.
    Seldin, M. F.
    Snyder, S.
    Tayek, J.
    Hernandez, E.
    LaPage, J.
    Garcia, C.
    Gonzalez, J.
    Aguilar, M.
    Klag, M.
    Parekh, R.
    Kao, L.
    Meoni, L.
    Whitehead, T.
    Chester, J.
    Knowler, W. C.
    Hanson, R. L.
    Nelson, R. G.
    Wolford, J.
    Jones, L.
    Juan, R.
    Lovelace, R.
    Luethe, C.
    Phillips, L. M.
    Sewemaenewa, J.
    Waseta, B.
    Saad, M. F.
    Nicholas, S. B.
    Chen, Y-D
    Guo, X.
    Rotter, J.
    Taylor, K.
    Budgett, M.
    Hariri, F.
    Zager, P.
    Scavini, M.
    Bobelu, A.
    Abboud, H.
    Arar, N.
    Duggirala, R.
    Kasinath, B. S.
    Thameem, F.
    Stern, M.
    Freedman, B.
    Bowden, D. W.
    Langefeld, C. D.
    Satko, S. C.
    Rich, S. S.
    Warren, S.
    Viverette, S.
    Brooks, G.
    Young, R.
    Spainhour, M.
    Winkler,Cheryl
    Smith, M. W.
    Thompson, M.
    Hanson, R.
    Kessing,Bailey
    Leehey, D. J.
    Barone, G.
    Thornley-Brown, D.
    Jefferson, C.
    Kohn, O. F.
    Brown, C. S.
    Briggs, J. P.
    Kimmel, P. L.
    Rasooly, R.
    Warnock, D.
    Cardon, L.
    Chakraborty, R.
    Dunston, G. M.
    Hostetter, T.
    O'Brien, S. J.
    Rioux, J.
    Spielman, R.

  2. Author Address

    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC 27101 USA.Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC 27101 USA.Wake Forest Sch Med, Dept Biochem, Winston Salem, NC 27157 USA.Wake Forest Sch Med, Dept Internal Med, Sect Nephrol, Winston Salem, NC USA.Wake Forest Sch Med, Dept Internal Med, Sect Endocrinol, Winston Salem, NC USA.Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA.Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA.Univ N Carolina, Dept Epidemiol, Gillings Sch Publ Hlth, Chapel Hill, NC 27515 USA.Loyola Univ Chicago, Dept Publ Hlth Sci, Div Nephrol & Hypertens, Maywood, IL USA.Loyola Univ Chicago, Dept Med, Div Nephrol & Hypertens, Maywood, IL USA.Hines Vet Affairs Med Ctr, Dept Med, Hines, IL USA.Wake Forest Sch Med, Ctr Publ Hlth Genom, Div Publ Hlth Sci, Winston Salem, NC USA.Wake Forest Sch Med, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC USA.Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.Univ Hlth Network, Hosp Sick Children, Dept Paediat, Toronto, ON, Canada.Univ Hlth Network, Hosp Sick Children, Dept Med, Toronto, ON, Canada.Univ Toronto, Toronto, ON, Canada.Northwestern Univ, Dept Prevent Med, Ctr Genet Med, Feinberg Sch Med, Chicago, IL 60611 USA.Harbor UCLA Med Ctr, Div Genom Outcomes, Dept Pediat, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA.Harbor UCLA Med Ctr, Div Genom Outcomes, Dept Med, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA.Cleveland Clin, Lerner Coll Med, Mol Med, Cleveland, OH 44106 USA.Cleveland Clin, Glickman Urol & Kidney Inst, Lerner Res Inst, Cleveland, OH 44106 USA.Univ Alabama Birmingham, Nephrol, Birmingham, AL USA.Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.Case Western Reserve Univ, Genet Anal & Data Coordinating Ctr, Cleveland, OH 44106 USA.Case Western Reserve Univ, Cleveland, OH 44106 USA.Harbor Univ Calif Los Angeles, Med Ctr, Los Angeles, CA USA.Johns Hopkins Univ, Baltimore, MD 21218 USA.NIDDK, Phoenix, AZ USA.Univ Calif Los Angeles, Los Angeles, CA 90024 USA.Univ New Mexico, Albuquerque, NM 87131 USA.Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.Wake Forest Univ, Winston Salem, NC 27109 USA.NCI, Lab Genom Divers, Frederick, MD 21701 USA.Loyola Univ, Minor Recruitment Ctr, New Orleans, LA 70118 USA.Univ Alabama Birmingham, Birmingham, AL USA.Univ Chicago, Chicago, IL 60637 USA.NIDDK Program Off, Phoenix, AZ USA.External Advisory Comm, Huntsville, AL USA.
    1. Year: 2019
    2. Date: MAY 15
  2. Journal: HUMAN GENOMICS
  3. BMC,
    1. 13
    2. 1
    3. Pages: pii: E482
  5. Type of Article: Article
  6. Article Number: 21
  7. ISSN: 1473-9542
  1. Abstract:

    BackgroundEnd-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.ResultsSix independent variants located in or near RND3/RBM43, SLITRK3, ENPP7, GNG7, and APOL1 achieved genome-wide significant association (P< 5x10(-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=9.84x10(-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=2.17x10(-8), OR=1.46) remained associated with all-cause ESKD in the APOL1-negative analysis.ConclusionsFindings provide further evidence for genetic factors associated with advanced kidney disease in AAs with T2D.

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External Sources

  1. View Full Text
  2. DOI: 10.1186/s40246-019-0205-7
  3. PMID: 31092297
  4. PMCID: PMC6521376
  5. View record in Web of Science®
  6. WOS: 000468167300001

Library Notes

  1. Fiscal Year: FY2018-2019
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