Researchers applied whole-genome sequencing to 1,052 unrelated people with congenital anomalies of the kidneys and urinary tract recruited to the UK's 100,000 Genomes Project, testing panel-based diagnostic yield alongside rare-variant and genome-wide association analyses. The single-gene diagnostic yield was 4.9%, rising to 11.1% in cystic kidney dysplasia, with family history, consanguinity and features outside the kidney each predicting a single-gene cause. Common and low-frequency variants were estimated to account for 23% of phenotypic variance (95% CI 1-45%), and a polygenic score for posterior urethral valves was validated in an independent cohort.
Why it is interesting: A national sequencing programme puts a low figure on what single-gene testing returns in a condition long treated as largely Mendelian.