Genome-wide linkage analysis of serum creatinine in three isolated European populations.
There is increasing evidence for a role of genetic predisposition in the etiology of kidney disease, but linkage scans have been poorly replicated. Here we performed a genome-wide linkage analysis of serum creatinine on 2859 individuals from isolated villages in South Tyrol (Italy), Rucphen (The Netherlands) and Vis Island (Croatia), populations that have been stable and permanently resident in their region. Linkage of serum creatinine levels to loci on chromosomes 7p14, 9p21, 11p15, 15q15-21, 16p13, and 18p11 was successfully replicated in at least one discovery population or in the pooled analysis. A novel locus was found on chromosome 10p11. Linkage to chromosome 22q13, independent of diabetes and hypertension, was detected over a region containing the non-muscle myosin heavy chain type II isoform A (MYH9) gene (LOD score=3.52). In non-diabetic individuals, serum creatinine was associated with this gene in two of the three populations and in meta-analysis (SNP rs11089788, P-value=0.0089). In populations sharing a homogeneous environment and genetic background, heritability of serum creatinine was higher than in outbred populations, with consequent detection of a larger number of loci than reported before. Our finding of a replicated association of serum creatinine with the MYH9 gene, recently linked to pathological renal conditions in African Americans, suggests that this gene may also influence kidney function in healthy Europeans.
Pattaro
Cristian
C
Institute of Genetic Medicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy.
Aulchenko
Yurii S
YS
Isaacs
Aaron
A
Vitart
Veronique
V
Hayward
Caroline
C
Franklin
Christopher S
CS
Polasek
Ozren
O
Kolcic
Ivana
I
Biloglav
Zrinka
Z
Campbell
Susan
S
Hastie
Nick
N
Lauc
Gordan
G
Meitinger
Thomas
T
Oostra
Ben A
BA
Gyllensten
Ulf
U
Wilson
James F
JF
Pichler
Irene
I
Hicks
Andrew A
AA
Campbell
Harry
H
Wright
Alan F
AF
Rudan
Igor
I
van Duijn
Cornelia M
CM
Riegler
Peter
P
Marroni
Fabio
F
Pramstaller
Peter P
PP
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003404:Creatinine / Q000097:blood*; D005060:Europe; D005260:Female; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D020409:Molecular Motor Proteins / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable; D044465:White People / Q000235:genetics; D055815:Young Adult
C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D003404:Creatinine; D018995:Myosin Heavy Chains