Human Genetics

, Volume 133, Issue 6, pp 769–779

Analysis of coding variants identified from exome sequencing resources for association with diabetic and non-diabetic nephropathy in African Americans

  • Jessica N. Cooke Bailey
  • Nicholette D. Palmer
  • Maggie C. Y. Ng
  • Jason A. Bonomo
  • Pamela J. Hicks
  • Jessica M. Hester
  • Carl D. Langefeld
  • Barry I. Freedman
  • Donald W. Bowden
Original Investigation

DOI: 10.1007/s00439-013-1415-z

Cite this article as:
Cooke Bailey, J.N., Palmer, N.D., Ng, M.C.Y. et al. Hum Genet (2014) 133: 769. doi:10.1007/s00439-013-1415-z

Abstract

Prior studies have identified common genetic variants influencing diabetic and non-diabetic nephropathy, diseases which disproportionately affect African Americans. Recently, exome sequencing techniques have facilitated identification of coding variants on a genome-wide basis in large samples. Exonic variants in known or suspected end-stage kidney disease (ESKD) or nephropathy genes can be tested for their ability to identify association either singly or in combination with known associated common variants. Coding variants in genes with prior evidence for association with ESKD or nephropathy were identified in the NHLBI-ESP GO database and genotyped in 5,045 African Americans (3,324 cases with type 2 diabetes associated nephropathy [T2D-ESKD] or non-T2D ESKD, and 1,721 controls) and 1,465 European Americans (568 T2D-ESKD cases and 897 controls). Logistic regression analyses were performed to assess association, with admixture and APOL1 risk status incorporated as covariates. Ten of 31 SNPs were associated in African Americans; four replicated in European Americans. In African Americans, SNPs in OR2L8, OR2AK2, C6orf167 (MMS22L), LIMK2, APOL3, APOL2, and APOL1 were nominally associated (P = 1.8 × 10−4–0.044). Haplotype analysis of common and coding variants increased evidence of association at the OR2L13 and APOL1 loci (P = 6.2 × 10−5 and 4.6 × 10−5, respectively). SNPs replicating in European Americans were in OR2AK2, LIMK2, and APOL2 (P = 0.0010-0.037). Meta-analyses highlighted four SNPs associated in T2D-ESKD and all-cause ESKD. Results from this study suggest a role for coding variants in the development of diabetic, non-diabetic, and/or all-cause ESKD in African Americans and/or European Americans.

Supplementary material

439_2013_1415_MOESM1_ESM.doc (96 kb)
Supplementary material 1 (DOC 95 kb)
439_2013_1415_MOESM2_ESM.doc (468 kb)
Supplementary material 2 (DOC 468 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Jessica N. Cooke Bailey
    • 1
    • 2
    • 3
  • Nicholette D. Palmer
    • 2
    • 3
    • 4
  • Maggie C. Y. Ng
    • 2
    • 3
  • Jason A. Bonomo
    • 1
    • 2
    • 3
  • Pamela J. Hicks
    • 2
    • 3
    • 4
  • Jessica M. Hester
    • 2
    • 3
    • 5
  • Carl D. Langefeld
    • 6
  • Barry I. Freedman
    • 7
  • Donald W. Bowden
    • 2
    • 3
    • 4
    • 8
  1. 1.Program in Molecular Medicine and Translational ScienceWake Forest School of MedicineWinston-SalemUSA
  2. 2.Center for Genomics and Personalized Medicine ResearchWake Forest School of MedicineWinston-SalemUSA
  3. 3.Center for Diabetes ResearchWake Forest School of MedicineWinston-SalemUSA
  4. 4.Department of BiochemistryWake Forest University School of MedicineWinston-SalemUSA
  5. 5.Molecular Genetics and Genomics ProgramWake Forest School of MedicineWinston-SalemUSA
  6. 6.Division of Public Health Sciences, Department of Biostatistical SciencesWake Forest School of MedicineWinston-SalemUSA
  7. 7.Section on Nephrology, Department of Internal MedicineWake Forest School of MedicineWinston-SalemUSA
  8. 8.Section on Endocrinology, Department of Internal MedicineWake Forest School of MedicineWinston-SalemUSA

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