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Candidate genes for non-diabetic ESRD in African Americans: a genome-wide association study using pooled DNA

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Abstract

African Americans have increased susceptibility to non-diabetic (non-DM) forms of end-stage renal disease (ESRD) and extensive evidence supports a genetic contribution. A genome-wide association study (GWAS) using pooled DNA was performed in 1,000 African Americans to detect associated genes. DNA from 500 non-DM ESRD cases and 500 non-nephropathy controls was quantified using gel electrophoresis and spectrophotometric analysis and pools of 50 case and 50 control DNA samples were created. DNA pools were genotyped in duplicate on the Illumina HumanHap550-Duo BeadChip. Normalization methods were developed and applied to array intensity values to reduce inter-array variance. Allele frequencies were calculated from normalized channel intensities and compared between case and control pools. Three SNPs had p values of <1.0E−6: rs4462445 (ch 13), rs4821469 (ch 22) and rs8077346 (ch 17). After normalization, top scoring SNPs (n = 65) were genotyped individually in 464 of the original cases and 478 of the controls, with replication in 336 non-DM ESRD cases and 363 non-nephropathy controls. Sixteen SNPs were associated with non-DM ESRD (p < 7.7E−4, Bonferroni corrected). Twelve of these SNPs are in or near the MYH9 gene. The four non-MYH9 SNPs that were associated with non-DM ESRD in the pooled samples were not associated in the replication set. Five SNPs that were modestly associated in the pooled samples were more strongly associated in the replication and/or combined samples. This is the first GWAS for non-DM ESRD in African Americans using pooled DNA. We demonstrate strong association between non-DM ESRD in African Americans with MYH9, and have identified additional candidate loci.

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Acknowledgments

This study was supported in part by NIH Grants R01 DK 070941 (BIF) and R01 DK53591 (DWB), and by the NIDDK and NCI Intramural Research Programs. MAB was supported by F32 DK080617 from the NIDDK. We gratefully acknowledge the contributions of the participants as well as the physicians who were part of the study and the work of our study coordinators Joyce Byers, Carrie Smith, Mitzie Spainhour, Cassandra Bethea, and Sharon Warren.

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Authors and Affiliations

  1. Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, 27157-1053, USA

    Meredith A. Bostrom, Pamela J. Hicks & Donald W. Bowden

  2. Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, 27157-1053, USA

    Lingyi Lu, Jeff Chou & Carl D. Langefeld

  3. Section on Nephrology, Department of Internal Medicine/Nephrology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1053, USA

    Barry I. Freedman

  4. Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, 27157-1053, USA

    Meredith A. Bostrom & Donald W. Bowden

  5. Center for Diabetes Research, Wake Forest University School of Medicine, Winston-Salem, NC, 27157-1053, USA

    Meredith A. Bostrom, Jianzhao Xu & Donald W. Bowden

Authors
  1. Meredith A. Bostrom
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  2. Lingyi Lu
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  3. Jeff Chou
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  4. Pamela J. Hicks
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  6. Carl D. Langefeld
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  7. Donald W. Bowden
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  8. Barry I. Freedman
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Correspondence to Barry I. Freedman.

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Bostrom, M.A., Lu, L., Chou, J. et al. Candidate genes for non-diabetic ESRD in African Americans: a genome-wide association study using pooled DNA. Hum Genet 128, 195–204 (2010). https://doi.org/10.1007/s00439-010-0842-3

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  • DOI: https://doi.org/10.1007/s00439-010-0842-3

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