ArticleNature communications2020
Polygenic background modifies penetrance of monogenic variants for tier 1 genomic conditions.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 271 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
271 citing papers in PubMed, 4 syntheses or guidelines pooled it, 464 citations in OpenAlex.
- Rare variant analyses in 51,256 type 2 diabetes cases and 370,487 controls reveal the pathogenicity spectrum of monogenic diabetes genes.Nature genetics · 2024Pooled it
- Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2023Guideline
- Genome-wide association and multi-trait analyses characterize the common genetic architecture of heart failure.Nature communications · 2022Pooled it
- The clinical utility of polygenic risk scores in genomic medicine practices: a systematic review.Human genetics · 2022Pooled it
- Genomic Medicine Sweden: Advancing precision medicine at the national level.Journal of internal medicine · 2026Review
- A heritability-optimized method for functional prioritization of rare coding variants in complex traits.Nature genetics · 2026Article
- Development and Validation of a Clinical Polygenic Risk Report in U.S.-Based Health Systems for 8 Cardiovascular Conditions.Journal of the American College of Cardiology · 2026Article
- Article
- Machine Learning Reveals the Contribution of Rare Genetic Variants and Enhances Risk Prediction for Coronary Artery Disease in the Japanese Population.Circulation. Genomic and precision medicine · 2026Article
- Recurrent Copy Number Variants and Psychiatric Outcomes in the Context of Polygenic Scores.JAMA psychiatry · 2026Article
- Inherited risk of coronary artery disease: redefining care with imaging and genetics.Nature reviews. Cardiology · 2026Review
- Uromodulin T62P variant causes kidney tubular stress and injury modulated by age and polygenic risk.medRxiv : the preprint server for health sciences · 2026Article
- Germline determinants of risk and molecular subtype in young-onset lung cancer.medRxiv : the preprint server for health sciences · 2026Article
- Individuals who deviate from polygenic expectation are enriched for damaging variants in genes linked to rare disease.American journal of human genetics · 2026Article
- Polygenic background contributes to GCK-MODY clinical presentation and glycaemic variability.Diabetologia · 2026Article
- Polygenic scores as modifiers in Mendelian diseases.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026Article
- Polygenic risk scores in clinical applications - opportunities and challenges.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026Article
- Polygenic risk scores in cancer.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026Article
- Improving Polygenic Risk Prediction for Atherosclerotic Cardiovascular Disease in East Asian Populations.JACC. Asia · 2026Review
- Review
211 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 5 institutions in 1 country.
Funding
Abstract
Genetic variation can predispose to disease both through (i) monogenic risk variants that disrupt a physiologic pathway with large effect on disease and (ii) polygenic risk that involves many variants of small effect in different pathways. Few studies have explored the interplay between monogenic and polygenic risk. Here, we study 80,928 individuals to examine whether polygenic background can modify penetrance of disease in tier 1 genomic conditions - familial hypercholesterolemia, hereditary breast and ovarian cancer, and Lynch syndrome. Among carriers of a monogenic risk variant, we estimate substantial gradients in disease risk based on polygenic background - the probability of disease by age 75 years ranged from 17% to 78% for coronary artery disease, 13% to 76% for breast cancer, and 11% to 80% for colon cancer. We propose that accounting for polygenic background is likely to increase accuracy of risk estimation for individuals who inherit a monogenic risk variant.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.