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

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.

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Correspondence to W H Linda Kao.

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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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