Genome-wide linkage and association study implicates the 10q26 region as a major genetic contributor to primary nonsyndromic vesicoureteric reflux
Year: 2017
Type: article
Study design: Observational Study
Abstract: Vesicoureteric reflux (VUR) is the commonest urological anomaly in children. Despite treatment improvements, associated renal lesions - congenital dysplasia, acquired scarring or both - are a common cause of childhood hypertension and renal failure. Primary VUR is familial, with transmission rate and sibling risk both approaching 50%, and appears highly genetically heterogeneous. It is often associated with other developmental anomalies of the urinary tract, emphasising its etiology as a disorder of urogenital tract development. We conducted a genome-wide linkage and association study in three European populations to search for loci predisposing to VUR. Family-based association analysis of 1098 parent-affected-child trios and case/control association analysis of 1147 cases and 3789 controls did not reveal any compelling associations, but parametric linkage analysis of 460 families (1062 affected individuals) under a dominant model identified a single region, on 10q26, that showed strong linkage (HLOD = 4.90; ZLRLOD = 4.39) to VUR. The ~9Mb region contains 69 genes, including some good biological candidates. Resequencing this region in selected individuals did not clearly implicate any gene but FOXI2, FANK1 and GLRX3 remain candidates for further investigation. This, the largest genetic study of VUR to date, highlights the 10q26 region as a major genetic contributor to VUR in European populations.
Source: Scientific Reports
Authors: John M. Darlow, Rebecca Darlay, Mark G. Dobson, Aisling Stewart, Pimphen Charoen, Jennifer Southgate, Simon C. Baker, Yaobo Xu, Manuela Hunziker, Heather J. Lambert, Andrew J. Green, Mauro Santibanez-Koref, John A. Sayer, Timothy H. J. Goodship, Prem Puri, Adrian S. Woolf, Rajko B. Kenda, David E. Barton, Heather J. Cordell
Institutions: Children's Health Ireland at Crumlin, National Children’s Research Centre, Newcastle University, Mahidol University, University College London, University of York, University Children's Hospital Zurich, Royal Victoria Infirmary, University College Dublin, Manchester Academic Health Science Centre, University of Manchester, Royal Manchester Children's Hospital, Ljubljana University Medical Centre
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,643
Awards: Development of statistical methodology for detection and characterisation of genetic factors in complex disease., Development and application of statistical methodology for the detection and characterisation of genetic factors in complex disease., A sibling pair study to identify the genes for vesicoureteric reflux., Development and application of statistical methodology for the detection and characterisation of genetic factors in complex disease., Development of statistical methodology for detection and characterisation of genetic factors in complex disease., G3602865887, The Avon Longitudinal Study of Parents and Children: An international resource for population
genomics and lifecourse epidemiology. Core Programme Support 2011-2015 and Core programme support 2014-2019, Molecular bases of congenital bladder disease: the urofacial syndome (UFS), Vesicoureteric reflux in the United Kingdom - establishing a DNA collection from affected families
OpenAlex ID: W2763977535