- Design
- Whole-genome sequencing cohort with genome-wide association
- Population
- 1,052 people with CAKUT in the UK 100,000 Genomes Project
- Primary outcome
- Monogenic diagnostic yield
- Effect
- 4.9% overall; consanguinity OR 3.0 (1.2–6.9) for monogenic diagnosis
A whole-genome sequencing study in Kidney International (21 September) analysed 1,052 unrelated people with congenital anomalies of the kidney and urinary tract (CAKUT) from the UK 100,000 Genomes Project.
A monogenic diagnosis was found in only 4.9% overall, rising to 7.4% in kidney agenesis or hypodysplasia and 11.1% in cystic dysplasia. Family history, consanguinity and features outside the kidney each roughly doubled to tripled the odds of a monogenic finding. Common and low-frequency variants explained an estimated 23% of variation, with wide uncertainty.
Genetic testing is worth targeting: in a patient with CAKUT and consanguinity, a family history or extra-renal anomalies, the yield is higher. Consanguinity is relevant in parts of India, where yields may differ from this UK cohort.
- Monogenic diagnosis was found in under 5% of CAKUT overall
- Yield was higher with cystic dysplasia or agenesis/hypodysplasia
- Family history, consanguinity and extra-renal features predicted a genetic cause
- Target genetic testing to those features; counsel families on low overall yield
Why it matters
It sets realistic expectations for families and helps target limited genomic resources.
The statistics, in plain English
The 23% heritability estimate has a 95% CI of 1% to 45%, so how much common variants contribute remains very uncertain.
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