Diverse ancestry whole-genome sequencing association study identifies <i>TBX5</i> and <i>PTK7</i> as susceptibility genes for posterior urethral valves.

ABSTRACT: Posterior urethral valves (PUV) are the commonest cause of end-stage renal disease in children, but the genetic architecture of this rare disorder remains unknown. We performed a sequencing-based genome-wide association study (seqGWAS) in 132 unrelated male PUV cases and 23,727 controls of diverse ancestry, identifying statistically significant associations with common variants at 12q24.21 (p=7.8 × 10^-12; OR 0.4) and rare variants at 6p21.1 (p=2.0 × 10^-8; OR 7.2), that were replicated in an independent European cohort of 395 cases and 4151 controls. Fine mapping and functional genomic data mapped these loci to the transcription factor TBX5 and planar cell polarity gene PTK7, respectively, the encoded proteins of which were detected in the developing urin

SUBMITTER: Chan MMY 

PROVIDER: S-EPMC9512401 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature