ArticleNature communications2022
Common genetic variation associated with Mendelian disease severity revealed through cryptic phenotype analysis.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Shared genetic basis and structure of syndromic and normal facial variation.American journal of human genetics · 2026Article
- Computational strategies for cross-species knowledge transfer.Nature methods · 2026Review
- Residual allelic activity likely underlies the low rates of disease expression for predicted loss-of-function variants in population-scale biobanks.American journal of human genetics · 2025Article
- Comorbidity Disease Pattern in Japanese Elderly Population: A Network-Based Analysis.Mayo Clinic proceedings. Innovations, quality & outcomes · 2025Article
- Establishing Best Practices for Clinical GWAS: Tackling Imputation and Data Quality Challenges.International journal of molecular sciences · 2025Review
- Unveiling Secondary Mutations in Blended Phenotypes: Dual ERCC4 and OTOA Pathogenic Variants Through WES Analysis.International journal of molecular sciences · 2024Article
- Syndrome-informed phenotyping identifies a polygenic background for achondroplasia-like facial variation in the general population.Nature communications · 2024Article
- Implications of mappings between International Classification of Diseases clinical diagnosis codes and Human Phenotype Ontology terms.JAMIA open · 2024Article
- The Genetic Variants Influencing Hypertension Prevalence Based on the Risk of Insulin Resistance as Assessed Using the Metabolic Score for Insulin Resistance (METS-IR).International journal of molecular sciences · 2024Article
- The Interaction and Implication of Stress-Induced Hyperglycemia and Cytokine Release Following Traumatic Injury: A Structured Scoping Review.Diagnostics (Basel, Switzerland) · 2024Article
- Computational strategies for cross-species knowledge transfer and translational biomedicine.ArXiv · 2024Article
- Syndrome-informed phenotyping identifies a polygenic background for achondroplasia-like facial variation in the general population.bioRxiv : the preprint server for biology · 2023Article
- Common genetic variation associated with Mendelian disease severity revealed through cryptic phenotype analysis.Nature communications · 2022Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
Clinical heterogeneity is common in Mendelian disease, but small sample sizes make it difficult to identify specific contributing factors. However, if a disease represents the severely affected extreme of a spectrum of phenotypic variation, then modifier effects may be apparent within a larger subset of the population. Analyses that take advantage of this full spectrum could have substantially increased power. To test this, we developed cryptic phenotype analysis, a model-based approach that infers quantitative traits that capture disease-related phenotypic variability using qualitative symptom data. By applying this approach to 50 Mendelian diseases in two cohorts, we identify traits that reliably quantify disease severity. We then conduct genome-wide association analyses for five of the inferred cryptic phenotypes, uncovering common variation that is predictive of Mendelian disease-related diagnoses and outcomes. Overall, this study highlights the utility of computationally-derived phenotypes and biobank-scale cohorts for investigating the complex genetic architecture of Mendelian diseases.
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Registered trials
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