Abstract
Genetic variation at the MYH9 locus is linked to the high incidence of focal segmental glomerulosclerosis (FSGS) and non-diabetic end-stage renal disease among African Americans. To further define risk alleles with FSGS we performed a genome-wide association analysis using more than one million single-nucleotide polymorphisms in 56 African-American and 61 European-American patients with biopsy-confirmed FSGS. Results were compared to 1641 European Americans and 1800 African Americans as unselected controls. While no association was observed in the cohort of European Americans, the case-control comparison of African Americans found variants within a 60 kb region of chromosome 22 containing part of the APOL1 and MYH9 genes associated with increased risk of FSGS. This region spans different linkage disequilibrium blocks, and variants associating with disease within this region are in linkage disequilibrium with variants which have shown signals of natural selection. APOL1 is a strong candidate for a gene that has undergone recent natural selection and is known to be involved in the infection by Trypanosoma brucei, a parasite common in Africa that has recently adapted to infect human hosts. Further studies will be required to establish which variants are causally related to kidney disease, what mutations caused the selective sweep, and to ultimately determine if these are the same.
Original language | English (US) |
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Pages (from-to) | 698-704 |
Number of pages | 7 |
Journal | Kidney international |
Volume | 78 |
Issue number | 7 |
DOIs | |
State | Published - Oct 2010 |
Bibliographical note
Funding Information:We thank the study subjects for their participation. This work was supported by grants from the NIH (NIH DK54931), Genzyme GRIP award (to MRP), RO1 HG003646 (to RL), and the JDRF (to SJT). MRP is an established investigator of the American Heart Association. We thank Drs Jeffrey Kopp, Cheryl Winkler, George Nelson, and David Friedman for helpful discussions.
Keywords
- end-stage kidney disease
- focal segmental glomerulosclerosis
- genetic renal disease