ArticleAmerican journal of human genetics2022
A spectrum of recessiveness among Mendelian disease variants in UK Biobank.
Article in American journal of human genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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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
38 citing papers in PubMed, 60 citations in OpenAlex.
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- Allele frequencies at recessive disease genes are mainly determined by pleiotropic effects in heterozygotes.Genetics · 2026Article
- Is Tori seeing red? A lesson for first-year biology that unveils the complexity of phenotypic variation with pedigree analysis.Journal of microbiology & biology education · 2026Article
- Genetic influences on haematopoiesis.Nature reviews. Genetics · 2026Review
- Respiratory Outcomes in Children With Neonatal Respiratory Distress Syndrome and Monoallelic ABCA3 Variants.Pediatric pulmonology · 2026Article
- Hypophosphatasia: low penetrance of pathogenic and likely-pathogenic ALPL variants identified through an unselected biorepository.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Article
- Rare heterozygous missense variants in VSX2 are associated with retinal detachment.PLoS genetics · 2026Article
- Whole-genome sequencing reveals rare and structural variants contributing to psoriasis and identifies CERCAM as a risk gene.Cell genomics · 2025Article
- Genotypic and phenotypic consequences of domestication in dogs.bioRxiv : the preprint server for biology · 2025Article
- Coagulation factor XII haploinsufficiency is protective against venous thromboembolism in a population-scale multidimensional analysis.Nature communications · 2025Article
- Reproductive and cognitive phenotypes in carriers of recessive pathogenic variants.Nature human behaviour · 2025Article
- Genome sequencing reveals CCDC88A variants in malformations of cortical development and immune dysfunction.Human molecular genetics · 2025Article
- Using large-scale population-based data to improve disease risk assessment of clinical variants.Nature genetics · 2025Review
- A Multiomic Network Approach to Uncover Disease Modifying Mechanisms of Inborn Errors of Metabolism.Journal of inherited metabolic disease · 2025Article
- Widespread recessive effects on common diseases in a cohort of 44,000 British Pakistanis and Bangladeshis with high autozygosity.American journal of human genetics · 2025Article
- CommonGenome research · 2025Article
- Coupling metabolomics and exome sequencing reveals graded effects of rare damaging heterozygous variants on gene function and human traits.Nature genetics · 2025Article
- Prequalification of genome-based newborn screening for severe childhood genetic diseases through federated training based on purifying hyperselection.American journal of human genetics · 2024Article
- Article
- Screening embryos for polygenic disease risk: a review of epidemiological, clinical, and ethical considerations.Human reproduction update · 2024Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Recent work has found increasing evidence of mitigated, incompletely penetrant phenotypes in heterozygous carriers of recessive Mendelian disease variants. We leveraged whole-exome imputation within the full UK Biobank cohort (n ∼ 500K) to extend such analyses to 3,475 rare variants curated from ClinVar and OMIM. Testing these variants for association with 58 quantitative traits yielded 102 significant associations involving variants previously implicated in 34 different diseases. Notable examples included a POR missense variant implicated in Antley-Bixler syndrome that associated with a 1.76 (SE 0.27) cm increase in height and an ABCA3 missense variant implicated in interstitial lung disease that associated with reduced FEV1/FVC ratio. Association analyses with 1,134 disease traits yielded five additional variant-disease associations. We also observed contrasting levels of recessiveness between two more-common, classical Mendelian diseases. Carriers of cystic fibrosis variants exhibited increased risk of several mitigated disease phenotypes, whereas carriers of spinal muscular atrophy alleles showed no evidence of altered phenotypes. Incomplete penetrance of cystic fibrosis carrier phenotypes did not appear to be mediated by common allelic variation on the functional haplotype. Our results show that many disease-associated recessive variants can produce mitigated phenotypes in heterozygous carriers and motivate further work exploring penetrance mechanisms.
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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.