A genome-wide scan for genes involved in primary vesicoureteric reflux

J Med Genet. 2007 Nov;44(11):710-7. doi: 10.1136/jmg.2007.051086. Epub 2007 Jul 27.

Abstract

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 and methods: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Child
  • DNA Mutational Analysis*
  • Female
  • Genetic Heterogeneity
  • Humans
  • Ireland / epidemiology
  • Lod Score
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Vesico-Ureteral Reflux / embryology
  • Vesico-Ureteral Reflux / epidemiology
  • Vesico-Ureteral Reflux / genetics*