ArticleGenetics in medicine : official journal of the American College of Medical Genetics2021
Positive predictive value highlights four novel candidates for actionable genetic screening from analysis of 220,000 clinicogenomic records.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 25 citations in OpenAlex.
- Hypertension increases PPV for polycystic kidney disease in PKD1 and PKD2 variant carriers.HGG advances · 2025Article
- Underestimated risk of secondary complications in pathogenic and glucose-elevating GCK variant carriers with type 2 diabetes.Communications medicine · 2024Article
- Exome sequencing identifies novel genetic variants associated with varicose veins.PLoS genetics · 2024Article
- Combining rare and common genetic variants improves population risk stratification for breast cancer.Genetics in medicine open · 2024Article
- Combined population genomic screening for three high-risk conditions in Australia: a modelling study.EClinicalMedicine · 2023Article
- A comprehensive map of human glucokinase variant activity.Genome biology · 2023Article
- Analysis of rare genetic variation underlying cardiometabolic diseases and traits among 200,000 individuals in the UK Biobank.Nature genetics · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo identify conditions that are candidates for population genetic screening based on population prevalence, penetrance of rare variants, and actionability.
methodsWe analyzed exome and medical record data from >220,000 participants across two large population health cohorts with different demographics. We performed a gene-based collapsing analysis of rare variants to identify genes significantly associated with disease status.
resultsWe identify 74 statistically significant gene-disease associations across 27 genes. Seven of these conditions have a positive predictive value (PPV) of at least 30% in both cohorts. Three are already used in population screening programs (BRCA1, BRCA2, LDLR), and we also identify four new candidates for population screening: GCK with diabetes mellitus, HBB with β-thalassemia minor and intermedia, PKD1 with cystic kidney disease, and MIP with cataracts. Importantly, the associations are actionable in that early genetic screening of each of these conditions is expected to improve outcomes.
conclusionWe identify seven genetic conditions where rare variation appears appropriate to assess in population screening, four of which are not yet used in screening programs. The addition of GCK, HBB, PKD1, and MIP rare variants into genetic screening programs would reach an additional 0.21% of participants with actionable disease risk, depending on the population.
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