Primary, nonsyndromic vesicoureteric reflux and its nephropathy is genetically heterogeneous, with a locus on chromosome 1

Primary vesicoureteric reflux (VUR) affects 1%-2% of whites, and reflux nep hropathy (RN) causes up to 15% of end-stage renal failure in children and a dults. There is a 30-50-fold increased incidence of WR in first-degree rela tives of probands, compared with the general population. We report the resu lts of the first genomewide search of VUR and RN; we studied seven European families whose members exhibit apparently dominant inheritance. We initial ly typed 387 polymorphic markers spaced, on average, at 10 cM throughout th e genome; we used the GENEHUNTER program to provide parametric and nonparam etric linkage analyses of affected individuals. The most positive locus spa nned 20 cM on 1p13 between GATA176C01 and D1S1653 and had a nonparametric L OD score (NPL) of 5.76 (P = .0002) and a parametric LOD score of 3.16. Satu ration with markers at 1-cM intervals increased the NPL to 5.94 (P = .00009 ). Hence, WR maps to a locus on chromosome 1. There was evidence of genetic heterogeneity at the chromosome 1 locus, and 12 additional loci were ident ified genomewide, with P < .05. No significant linkage was found to Gp, whe re a renal and ureteric malformation locus has been reported, or to PAX2, m utations of which cause WR in renal-coloboma syndrome. Our results support the hypothesis that WR is a genetic disorder.