ArticleNature genetics2024
Genetic modifiers of rare variants in monogenic developmental disorder loci.
Article in Nature genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Rare-Variant Genome-Wide Association and Polygenic Score Assessment of Vitamin D Status in a Middle Eastern Population.International journal of molecular sciences · 2025Pooled it
- Imputation of fluid intelligence scores reduces ascertainment bias and increases power for analyses of common and rare variants.Nature genetics · 2026Article
- Article
- Shared genetic basis and structure of syndromic and normal facial variation.American journal of human genetics · 2026Article
- Common and rare genetic variant associations with cognitive performance across development in British birth cohorts.Nature human behaviour · 2026Article
- Analysis of rare coding variants in schizophrenia-associated genes and generalised cognition in the UK Biobank.Molecular psychiatry · 2026Article
- Best practice recommendations for bioinformatics approaches applied to high-throughput sequencing for rare disease and cancer diagnosis within the UK National Health Service.Journal of medical genetics · 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
- Pediatric Genomic Medicine-rapid progress, but not too fast: American Pediatric Society's 2026 John Howland Award Lecture.Pediatric research · 2026Article
- Inference of elevated mutation rates and variant effects using 700k exomes.bioRxiv : the preprint server for biology · 2026Article
- Decomposing the genetic risk of autism spectrum disorder into discrete molecular subtypes underlie clinical heterogeneity based on transcriptome profile.Journal of translational medicine · 2026Article
- Article
- Functional impact of genetic background on variable expressivity in neurodevelopmental disorders.Nature communications · 2026Article
- Transcriptomic and phenotypic convergence of neurodevelopmental disorder risk genes in vitro and in vivo.Nature neuroscience · 2026Article
- Combinatorial effects of gene dosage, polygenic background and environment on complex traits.medRxiv : the preprint server for health sciences · 2026Article
- Missense variants in DPYSL5 associated with neurodevelopmental disorders and brain malformations cause impaired neuronal maturation in vitro.Molecular psychiatry · 2026Article
- Co-occurrence of rare variants implicates gene pairs in cytoskeletal pathways and is associated with increased severity in autism spectrum disorder.Genome biology · 2026Article
- Expanding the scope of human immunology in theJournal of human immunity · 2026Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Rare damaging variants in a large number of genes are known to cause monogenic developmental disorders (DDs) and have also been shown to cause milder subclinical phenotypes in population cohorts. Here, we show that carrying multiple (2-5) rare damaging variants across 599 dominant DD genes has an additive adverse effect on numerous cognitive and socioeconomic traits in UK Biobank, which can be partially counterbalanced by a higher educational attainment polygenic score (EA-PGS). Phenotypic deviators from expected EA-PGS could be partly explained by the enrichment or depletion of rare DD variants. Among carriers of rare DD variants, those with a DD-related clinical diagnosis had a substantially lower EA-PGS and more severe phenotype than those without a clinical diagnosis. Our results suggest that the overall burden of both rare and common variants can modify the expressivity of a phenotype, which may then influence whether an individual reaches the threshold for clinical disease.
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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.