ArticleGenetic epidemiology2019
Loss of function, missense, and intronic variants in NOTCH1 confer different risks for left ventricular outflow tract obstructive heart defects in two European cohorts.
Article in Genetic epidemiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Genome-wide association studies highlight novel risk loci for septal defects and left-sided congenital heart defects.BMC genomics · 2024Pooled it
- Diagnostic Yield of Exome Sequencing in Patients With Congenital Heart Disease From Southern Africa.Circulation. Genomic and precision medicine · 2026Article
- Hypoplastic Left Heart Syndrome Cardiomyocytes Exhibit Intrinsic Stress Vulnerabilities and Augmented Stress Responses in vitro.Stem cell reviews and reports · 2026Article
- Functional annotation of non-coding variants identifies a novel enhancer with activity in neural crest cell-derived lineages.Research square · 2026Article
- Genetic variation in NOTCH1 is associated with overweight and obesity in Brazilian elderly.Scientific reports · 2024Article
- Expanding the phenotypic spectrum of NOTCH1 variants: clinical manifestations in families with congenital heart disease.European journal of human genetics : EJHG · 2024Article
- Human Genetics of Semilunar Valve and Aortic Arch Anomalies.Advances in experimental medicine and biology · 2024Review
- Clinical risk associated with COVID-19 among 86000 patients with congenital heart disease.Open heart · 2023Article
- Considering the Genetic Architecture of Hypoplastic Left Heart Syndrome.Journal of cardiovascular development and disease · 2022Article
- A Phenotype and Genotype Case Report of a Neonate With Congenital Bilateral Coronary Artery Fistulas and Multiple Collateral Arteries.Frontiers in cardiovascular medicine · 2022Article
- Review
- Genetic Etiology of Left-Sided Obstructive Heart Lesions: A Story in Development.Journal of the American Heart Association · 2021Review
- Prenatal Genetic Diagnosis in Three Fetuses With Left Heart Hypoplasia (LHH) From Three Unrelated Families.Frontiers in cardiovascular medicine · 2021Article
- Novel loss of function mutation in NOTCH1 in a family with bicuspid aortic valve, ventricular septal defect, thoracic aortic aneurysm, and aortic valve stenosis.Molecular genetics & genomic medicine · 2020Article
- A novel de novo dominant mutation of NOTCH1 gene in an Iranian family with non-syndromic congenital heart disease.Journal of clinical laboratory analysis · 2020Article
- Functional genomics and gene-environment interaction highlight the complexity of congenital heart disease caused by Notch pathway variants.Human molecular genetics · 2020Article
- Genes and Pathways Implicated in Tetralogy of Fallot Revealed by Ultra-Rare Variant Burden Analysis in 231 Genome Sequences.Frontiers in genetics · 2020Article
- Rare Variants in Genes Associated With Cardiomyopathy Are Not Common in Hypoplastic Left Heart Syndrome Patients With Myocardial Dysfunction.Frontiers in pediatrics · 2020Article
- Genetics of Congenital Heart Disease.Biomolecules · 2019Review
- Association between the 4p16 genomic locus and different types of congenital heart disease: results from adult survivors in the UK Biobank.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
Loss of function variants in NOTCH1 cause left ventricular outflow tract obstructive defects (LVOTO). However, the risk conferred by rare and noncoding variants in NOTCH1 for LVOTO remains largely uncharacterized. In a cohort of 49 families affected by hypoplastic left heart syndrome, a severe form of LVOTO, we discovered predicted loss of function NOTCH1 variants in 6% of individuals. Rare or low-frequency missense variants were found in 16% of families. To make a quantitative estimate of the genetic risk posed by variants in NOTCH1 for LVOTO, we studied associations of 400 coding and noncoding variants in NOTCH1 in 1,085 cases and 332,788 controls from the UK Biobank. Two rare intronic variants in strong linkage disequilibrium displayed significant association with risk for LVOTO amongst European-ancestry individuals. This result was replicated in an independent analysis of 210 cases and 68,762 controls of non-European and mixed ancestry. In conclusion, carrying rare predicted loss of function variants in NOTCH1 confer significant risk for LVOTO. In addition, the two intronic variants seem to be associated with an increased risk for these defects. Our approach demonstrates the utility of population-based data sets in quantifying the specific risk of individual variants for disease-related phenotypes.
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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.