MYH9 is associated with nondiabetic end-stage renal disease in African Americans.
As end-stage renal disease (ESRD) has a four times higher incidence in African Americans compared to European Americans, we hypothesized that susceptibility alleles for ESRD have a higher frequency in the West African than the European gene pool. We carried out a genome-wide admixture scan in 1,372 ESRD cases and 806 controls and found a highly significant association between excess African ancestry and nondiabetic ESRD (lod score = 5.70) but not diabetic ESRD (lod = 0.47) on chromosome 22q12. Each copy of the European ancestral allele conferred a relative risk of 0.50 (95% CI = 0.39-0.63) compared to African ancestry. Multiple common SNPs (allele frequencies ranging from 0.2 to 0.6) in the gene encoding nonmuscle myosin heavy chain type II isoform A (MYH9) were associated with two to four times greater risk of nondiabetic ESRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans.
Kao
W H Linda
WH
Department of Epidemiology, School of Medicine and Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21287, USA. wkao@jhsph.edu
Klag
Michael J
MJ
Meoni
Lucy A
LA
Reich
David
D
Berthier-Schaad
Yvette
Y
Li
Man
M
Coresh
Josef
J
Patterson
Nick
N
Tandon
Arti
A
Powe
Neil R
NR
Fink
Nancy E
NE
Sadler
John H
JH
Weir
Matthew R
MR
Abboud
Hanna E
HE
Adler
Sharon G
SG
Divers
Jasmin
J
Iyengar
Sudha K
SK
Freedman
Barry I
BI
Kimmel
Paul L
PL
Knowler
William C
WC
Kohn
Orly F
OF
Kramp
Kristopher
K
Leehey
David J
DJ
Nicholas
Susanne B
SB
Pahl
Madeleine V
MV
Schelling
Jeffrey R
JR
Sedor
John R
JR
Thornley-Brown
Denyse
D
Winkler
Cheryl A
CA
Smith
Michael W
MW
Parekh
Rulan S
RS
D001741:Black or African American / Q000235:genetics; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D015331:Cohort Studies; D017931:DNA Primers / Q000737:chemistry; D003920:Diabetes Mellitus / Q000235:genetics* / Q000473:pathology; 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; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000473:pathology; 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*; D011446:Prospective Studies; 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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