Article abstract
Nature Genetics 40, 1185 - 1192 (2008)
Published online: 14 September 2008 | doi:10.1038/ng.232
MYH9 is associated with nondiabetic end-stage renal disease in African Americans
W H Linda Kao1,2,3,25, Michael J Klag1,2,3,25, Lucy A Meoni2,3,4, David Reich5,6, Yvette Berthier-Schaad1, Man Li1, Josef Coresh1,2,3,4, Nick Patterson6, Arti Tandon5,6, Neil R Powe1,2,3, Nancy E Fink1,2,3, John H Sadler7, Matthew R Weir7, Hanna E Abboud8, Sharon G Adler9, Jasmin Divers10, Sudha K Iyengar11, Barry I Freedman10, Paul L Kimmel12, William C Knowler13, Orly F Kohn14, Kristopher Kramp11, David J Leehey15, Susanne B Nicholas16, Madeleine V Pahl17, Jeffrey R Schelling18, John R Sedor18,19, Denyse Thornley-Brown20, Cheryl A Winkler21, Michael W Smith21,24 & Rulan S Parekh1,2,3,22, on behalf of the Family Investigation of Nephropathy and Diabetes (FIND) Research Group23
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.
- Department of Epidemiology, School of Medicine and Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21287, USA.
- Department of Medicine, School of Medicine and Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21287, USA.
- The Welch Center for Prevention, Epidemiology, and Clinical Research, School of Medicine and Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21287, USA.
- Department of Biostatistics, School of Medicine and Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21287, USA.
- Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
- Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
- Department of Medicine, University of Maryland, Baltimore, Maryland 21201, USA.
- Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.
- Department of Medicine, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Los Angeles, California 90502, USA.
- Department of Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
- Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44109, USA.
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
- Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Disease, National Institute of Health, Phoenix, Arizona 85014, USA.
- Department of Medicine, Loyola University of Chicago, Chicago, Illinois 60153, USA.
- Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA.
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90024, USA.
- Department of Medicine, University of California Irvine, Irvine, California 92868, USA.
- Departments of Medicine, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44109, USA.
- Biophysiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44109, USA.
- Department of Medicine, University of Alabama, Birmingham, Alabama 35294, USA.
- Laboratory of Genomic Diversity, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland 21702, USA.
- Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA.
- A full list of members is provided in the Supplementary Note online.
- Present address: Genetics and Genomics, Advanced Technology Program, SAIC-Frederick, National Cancer Institute, Frederick, Maryland 21701, USA.
- These authors contributed equally to this work.
Correspondence to: W H Linda Kao1,2,3,25 e-mail: wkao@jhsph.edu
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