ArticleNature communications2019
Quantifying the polygenic contribution to variable expressivity in eleven rare genetic disorders.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 2 of them syntheses that pooled it.
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Who cites it
75 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- 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
- Pooled it
- Shared genetic basis and structure of syndromic and normal facial variation.American journal of human genetics · 2026Article
- Contribution of Copy Number Variants and Cumulative Genetic Load to Autism Spectrum Disorders: Integrative Insights from Chromosomal Microarray Analysis.International journal of molecular 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
- Review
- Whole Genome Sequencing Reveals amedRxiv : the preprint server for health sciences · 2026Article
- Polygenic backgrounds influence phenotypic consequences of variants in cells, individuals, and populations.Cell genomics · 2026Review
- Individuals whose phenotype deviates from genetic expectation defined by common variation are enriched for rare damaging variants in genes that cause rare disease.medRxiv : the preprint server for health sciences · 2025Article
- Article
- Identification of a NovelDiagnostics (Basel, Switzerland) · 2025Article
- Common and rare genetic variants explain distinct diagnostic variance in pediatric attention deficit hyperactivity disorder.Genetics in medicine : official journal of the American College of Medical Genetics · 2025Article
- Influence of Polygenic Risk on Height and BMI in Adults With a 22q11.2 Microdeletion.Journal of the Endocrine Society · 2025Article
- Secondary findings in pediatric genomic testing: clinical insights from Turkey.European journal of pediatrics · 2025Article
- Investigating the sources of variable impact of pathogenic variants in monogenic metabolic conditions.Nature communications · 2025Article
- X and Y gene dosage effects are primary contributors to human sexual dimorphism: The case of height.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Astrocyte Reactivity Polygenic Risk Score May Predict Cognitive Decline in Alzheimer's Disease.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2025Article
- The proprotein convertase FURIN is a novel aneurysm predisposition gene impairing TGF-β signalling.Cardiovascular research · 2024Article
- The pleiotropic spectrum of proximal 16p11.2 CNVs.American journal of human genetics · 2024Review
- Complex trait associations in rare diseases and impacts on Mendelian variant interpretation.Nature communications · 2024Article
15 more citing papers are in PubMed but not listed here.
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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
Rare genetic disorders (RGDs) often exhibit significant clinical variability among affected individuals, a disease characteristic termed variable expressivity. Recently, the aggregate effect of common variation, quantified as polygenic scores (PGSs), has emerged as an effective tool for predictions of disease risk and trait variation in the general population. Here, we measure the effect of PGSs on 11 RGDs including four sex-chromosome aneuploidies (47,XXX; 47,XXY; 47,XYY; 45,X) that affect height; two copy-number variant (CNV) disorders (16p11.2 deletions and duplications) and a Mendelian disease (melanocortin 4 receptor deficiency (MC4R)) that affect BMI; and two Mendelian diseases affecting cholesterol: familial hypercholesterolemia (FH; LDLR and APOB) and familial hypobetalipoproteinemia (FHBL; PCSK9 and APOB). Our results demonstrate that common, polygenic factors of relevant complex traits frequently contribute to variable expressivity of RGDs and that PGSs may be a useful metric for predicting clinical severity in affected individuals and for risk stratification.
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