A genome-wide scan for genes involved in primary vesicoureteric reflux.
BACKGROUND
Vesicoureteric reflux (VUR) is the retrograde flow of urine from the bladder into the ureters. It is the most common urological anomaly in children, and a major cause of end-stage renal failure and hypertension in both children and adults. VUR is seen in approximately 1-2% of Caucasian newborns and is frequently familial.


OBJECTIVE
In order to search for genetic loci involved in VUR, we performed a genome-wide linkage scan using 4710 single-nucleotide polymorphisms (SNPs) in 609 individuals from 129 Irish families with >1 affected member.


RESULTS
Nonparametric linkage (NPL) analysis of the dataset yielded moderately suggestive linkage at chromosome 2q37 (NPL(max) = 2.67, p<0.001). Analysis of a subset without any additional features, such as duplex kidneys, yielded a maximum NPL score of 4.1 (p = 0.001), reaching levels of genome-wide statistical significance. Suggestive linkage was also seen at 10q26 and 6q27, and there were several smaller peaks.


CONCLUSIONS
Our results confirm the previous conclusion that VUR is genetically heterogeneous, and support the identification of several disease-associated regions indicated by smaller studies, as well as indicating new regions of interest for investigation.
Kelly
H
H
The National Centre for Medical Genetics, University College Dublin Department of Medical Genetics, Our Lady's Children's Hospital Crumlin, Dublin 12, Ireland.
Molony
C M
CM
Darlow
J M
JM
Pirker
M E
ME
Yoneda
A
A
Green
A J
AJ
Puri
P
P
Barton
D E
DE
D000328:Adult; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D007494:Ireland / Q000453:epidemiology; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014718:Vesico-Ureteral Reflux / Q000196:embryology / Q000453:epidemiology / Q000235:genetics*