NDT Advance Access originally published online on February 8, 2005
Nephrology Dialysis Transplantation 2005 20(4):712-718; doi:10.1093/ndt/gfh704
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A genome scan for all-cause end-stage renal disease in African Americans
1 Department of Internal Medicine, 2 Center for Human Genomics, 3 Department of Biochemistry and 4 Department of Public Health Sciences, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA
Correspondence and offprint requests to: Barry I. Freedman, MD, Department of Internal Medicine/Section on Nephrology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1053, USA. Email: bfreedma{at}wfubmc.edu
Background. In an attempt to map the genes predisposing to the common, complex aetiologies of end-stage renal disease (ESRD), we performed a genome-wide scan in 1023 individuals with chronic kidney disease (946 dialysis dependent and 77 with advanced chronic renal failure) from 483 African American families.
Methods. The study sample comprised 563 ESRD-affected sibling pairs, with nephropathy attributed to diabetes mellitus, chronic glomerular disease or hypertension. Multipoint non-parametric linkage (NPL) analysis methods were employed.
Results. NPL regression provided modest evidence of linkage to 13q33.3 near D13S796 [log of the odds (LOD) = 1.72], 9q34.3 near D9S1826 (LOD = 1.22), 4p15.32 near D4S2639 (LOD = 1.11) and 1q25.1 near D1S1589 (LOD = 1.01). Adjusting for the evidence of linkage at the other loci using NPL regression analysis provided evidence for linkage to 4p15.32, 9q34.3 and 13q33.3. NPL regression interaction and ordered subset analysis (OSA) suggested that the evidence for linkage to ESRD significantly increased with higher body mass index (BMI) at 13q33.3 (LOD = 4.94 in 61% of families with the highest BMI). Additionally, OSA suggested that linkage significantly improved in the 13% of families with earliest age at ESRD onset (LOD = 3.05 at 2q32.1) and in the 16% of families with latest age at ESRD onset (LOD = 2.47 at 10q26.3).
Conclusions. Multipoint single-locus linkage analysis provided modest evidence of linkage to all-cause ESRD in African Americans on 13q33.3, and NPL regression and OSA suggested that evidence for linkage in this region markedly increased in obese families. This region, as well as 9q34.3, 4p15.32 and 1q25.1, should receive priority in the search for loci contributing to ESRD susceptibility in African Americans.
Keywords: African American; diabetic nephropathy; end-stage renal disease; genome scan; hypertensive nephrosclerosis; linkage analysis
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