MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis.
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.
Kopp
Jeffrey B
JB
Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Smith
Michael W
MW
Nelson
George W
GW
Johnson
Randall C
RC
Freedman
Barry I
BI
Bowden
Donald W
DW
Oleksyk
Taras
T
McKenzie
Louise M
LM
Kajiyama
Hiroshi
H
Ahuja
Tejinder S
TS
Berns
Jeffrey S
JS
Briggs
William
W
Cho
Monique E
ME
Dart
Richard A
RA
Kimmel
Paul L
PL
Korbet
Stephen M
SM
Michel
Donna M
DM
Mokrzycki
Michele H
MH
Schelling
Jeffrey R
JR
Simon
Eric
E
Trachtman
Howard
H
Vlahov
David
D
Winkler
Cheryl A
CA
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
D017931:DNA Primers; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains
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