title: A risk allele for focal segmental glomerulosclerosis in African Americans is located within a region containing APOL1 and MYH9.
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.
authors.affiliation: Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Giulio
authors.initials: G
authors.lastname: Genovese
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Tonna
authors.forename: Andrea U
authors.initials: AU
authors.lastname: Knob
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Appel
authors.forename: Avi
authors.initials: A
authors.lastname: Katz
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Bernhardy
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Needham
authors.forename: Ross
authors.initials: R
authors.lastname: Lazarus
authors.forename: Martin R
authors.initials: MR
authors.lastname: Pollak
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000483:Alleles; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008075:Lipoproteins, HDL / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020409:Molecular Motor Proteins / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains