title: MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis.
abstract: The increased burden of chronic kidney and end-stage kidney diseases (ESKD) in populations of African ancestry has been largely unexplained. To identify genetic variants predisposing to idiopathic and HIV-1-associated focal segmental glomerulosclerosis (FSGS), we carried out an admixture-mapping linkage-disequilibrium genome scan on 190 African American individuals with FSGS and 222 controls. We identified a chromosome 22 region with a genome-wide logarithm of the odds (lod) score of 9.2 and a peak lod of 12.4 centered on MYH9, a functional candidate gene expressed in kidney podocytes. Multiple MYH9 SNPs and haplotypes were recessively associated with FSGS, most strongly a haplotype spanning exons 14 through 23 (OR = 5.0, 95% CI = 3.5-7.1; P = 4 x 10(-23), n = 852). This association extended to hypertensive ESKD (OR = 2.2, 95% CI = 1.5-3.4; n = 433), but not type 2 diabetic ESKD (n = 476). Genetic variation at the MYH9 locus substantially explains the increased burden of FSGS and hypertensive ESKD among African Americans.
authors.affiliation: Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Kopp
authors.forename: Michael W
authors.initials: MW
authors.lastname: Smith
authors.forename: George W
authors.initials: GW
authors.lastname: Nelson
authors.forename: Randall C
authors.initials: RC
authors.lastname: Johnson
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
authors.forename: Taras
authors.initials: T
authors.lastname: Oleksyk
authors.forename: Louise M
authors.initials: LM
authors.lastname: McKenzie
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kajiyama
authors.forename: Tejinder S
authors.initials: TS
authors.lastname: Ahuja
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Berns
authors.forename: William
authors.initials: W
authors.lastname: Briggs
authors.forename: Monique E
authors.initials: ME
authors.lastname: Cho
authors.forename: Richard A
authors.initials: RA
authors.lastname: Dart
authors.forename: Paul L
authors.initials: PL
authors.lastname: Kimmel
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Korbet
authors.forename: Donna M
authors.initials: DM
authors.lastname: Michel
authors.forename: Michele H
authors.initials: MH
authors.lastname: Mokrzycki
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Schelling
authors.forename: Eric
authors.initials: E
authors.lastname: Simon
authors.forename: Howard
authors.initials: H
authors.lastname: Trachtman
authors.forename: David
authors.initials: D
authors.lastname: Vlahov
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Winkler
mesh_terms: D016263:AIDS-Associated Nephropathy / Q000235:genetics; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics* / Q000473:pathology; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000235:genetics; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D020409:Molecular Motor Proteins / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D017931:DNA Primers; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains
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