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MYH9 is associated with nondiabetic end-stage renal disease in African Americans

Nature Genetics volume 40, pages 1185–1192 (2008)Cite this article

Abstract

As end-stage renal disease (ESRD) has a four times higher incidence in African Americans compared to European Americans, we hypothesized that susceptibility alleles for ESRD have a higher frequency in the West African than the European gene pool. We carried out a genome-wide admixture scan in 1,372 ESRD cases and 806 controls and found a highly significant association between excess African ancestry and nondiabetic ESRD (lod score = 5.70) but not diabetic ESRD (lod = 0.47) on chromosome 22q12. Each copy of the European ancestral allele conferred a relative risk of 0.50 (95% CI = 0.39–0.63) compared to African ancestry. Multiple common SNPs (allele frequencies ranging from 0.2 to 0.6) in the gene encoding nonmuscle myosin heavy chain type II isoform A (MYH9) were associated with two to four times greater risk of nondiabetic ESRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans.

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Figure 1: Summary of admixture scan results.
Figure 2: Region of association with nondiabetic ESRD on chromosome 22.
Figure 3: Effect of MYH9 SNPs on the association between local ancestry in the region of chromosome 22q12 and nondiabetic ESRD.

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Acknowledgements

We thank the study participants, staff, laboratories and physicians who participated in the FIND and the CHOICE Study at Dialysis Clinic, Inc. and at Johns Hopkins University. This study was also supported by the following research grants: U01DK070657, U01DK57304, K01DK067207 (W.H.L.K.), U01DK57292, and DK07024 (the CHOICE study) from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and, in part, by the Intramural Research Program of the NIDDK. The CHOICE study was also supported in part by HS08365 from the Agency for Healthcare Research and Quality, Rockville, Maryland and HL62985 from the National Heart Lung and Blood Institute, Bethesda, Maryland. This work was supported by the National Center for Research Resources for the General Clinical Research Center (GCRC) grants: Case Western Reserve University M01-RR-000080; Wake Forest University M01-RR-07122; Harbor-UCLA Medical Center M01-RR-00425; College of Medicine - University of California Irvine M01-RR-00827-29; Frederic C. Bartter M01-RR-01346. D.R. was supported by a Burroughs Wellcome Career Development Award in the Biomedical Sciences.

This research was supported in part by the Intramural Research Program of the US National Institutes of Health, National Cancer Institute, Center for Cancer Research. This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does it mention of trade names, commercial products, or organizations imply endorsement by the US government.

Author information

Author notes

  1. Michael W Smith

    Present address: Present address: Genetics and Genomics, Advanced Technology Program, SAIC-Frederick, National Cancer Institute, Frederick, Maryland 21701, USA.,

  2. W H Linda Kao and Michael J Klag: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Epidemiology, School of Medicine and Bloomberg School of Public Health, Johns Hopkins University, Baltimore, 21287, Maryland, USA

    W H Linda Kao, Michael J Klag, Yvette Berthier-Schaad, Man Li, Josef Coresh, Neil R Powe, Nancy E Fink & Rulan S Parekh

  2. Department of Medicine, School of Medicine and Bloomberg School of Public Health, Johns Hopkins University, Baltimore, 21287, Maryland, USA

    W H Linda Kao, Michael J Klag, Lucy A Meoni, Josef Coresh, Neil R Powe, Nancy E Fink & Rulan S Parekh

  3. The Welch Center for Prevention, Epidemiology, and Clinical Research, School of Medicine and Bloomberg School of Public Health, Johns Hopkins University, Baltimore, 21287, Maryland, USA

    W H Linda Kao, Michael J Klag, Lucy A Meoni, Josef Coresh, Neil R Powe, Nancy E Fink & Rulan S Parekh

  4. Department of Biostatistics, School of Medicine and Bloomberg School of Public Health, Johns Hopkins University, Baltimore, 21287, Maryland, USA

    Lucy A Meoni & Josef Coresh

  5. Department of Genetics, Harvard Medical School, Boston, 02115, Massachusetts, USA

    David Reich & Arti Tandon

  6. Broad Institute of Harvard and MIT, Cambridge, 02142, Massachusetts, USA

    David Reich, Nick Patterson & Arti Tandon

  7. Department of Medicine, University of Maryland, Baltimore, 21201, Maryland, USA

    John H Sadler & Matthew R Weir

  8. Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, 78229, Texas, USA

    Hanna E Abboud

  9. Department of Medicine, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Los Angeles, 90502, California, USA

    Sharon G Adler

  10. Department of Medicine, Wake Forest University School of Medicine, Winston-Salem, 27157, North Carolina, USA

    Jasmin Divers & Barry I Freedman

  11. Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, 44109, Ohio, USA

    Sudha K Iyengar & Kristopher Kramp

  12. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Paul L Kimmel

  13. Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Disease, National Institute of Health, Phoenix, 85014, Arizona, USA

    William C Knowler

  14. Department of Medicine, Loyola University of Chicago, Chicago, 60153, Illinois, USA

    Orly F Kohn

  15. Department of Medicine, University of Chicago, Chicago, 60637, Illinois, USA

    David J Leehey

  16. Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, 90024, California, USA

    Susanne B Nicholas

  17. Department of Medicine, University of California Irvine, Irvine, 92868, California, USA

    Madeleine V Pahl

  18. Departments of Medicine, School of Medicine, Case Western Reserve University, Cleveland, 44109, Ohio, USA

    Jeffrey R Schelling & John R Sedor

  19. Biophysiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, 44109, Ohio, USA

    John R Sedor

  20. Department of Medicine, University of Alabama, Birmingham, 35294, Alabama, USA

    Denyse Thornley-Brown

  21. Laboratory of Genomic Diversity, SAIC-Frederick, Inc., NCI-Frederick, Frederick, 21702, Maryland, USA

    Cheryl A Winkler & Michael W Smith

  22. Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, 21287, Maryland, USA

    Rulan S Parekh

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on behalf of the Family Investigation of Nephropathy and Diabetes (FIND) Research Group

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Correspondence to W H Linda Kao.

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A full list of members is provided in the Supplementary Note.

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Kao, W., Klag, M., Meoni, L. et al. MYH9 is associated with nondiabetic end-stage renal disease in African Americans. Nat Genet 40, 1185–1192 (2008). https://doi.org/10.1038/ng.232

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