ArticleAmerican journal of human genetics2012
An excess of deleterious variants in VEGF-A pathway genes in Down-syndrome-associated atrioventricular septal defects.
Article in American journal of human genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 2 of them syntheses that pooled it.
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
62 citing papers in PubMed, 2 syntheses or guidelines pooled it, 119 citations in OpenAlex.
- Meta-Analysis of Genome-Wide Association Studies Reveals Genetic Mechanisms of Supraventricular Arrhythmias.Circulation. Genomic and precision medicine · 2024Pooled it
- Gender differences in the prevalence of congenital heart disease in Down's syndrome: a brief meta-analysis.BMC medical genetics · 2017Pooled it
- Trial
- First- and Second-Trimester Cardiovascular Anomalies in Trisomy 21 Fetuses: Anatomy, Embryology, Genetics and Imaging.Journal of personalized medicine · 2026Review
- Increased methylation levels of theEpigenomics · 2025Article
- A multicenter observational cohort study in survivors of Down Syndrome-associated acute leukemia (ALTE22C1): a report from the Children's Oncology Group.BMC cancer · 2025Observational
- Cyclin-dependent kinase 13 is indispensable for normal mouse heart development.Journal of anatomy · 2025Article
- Deciphering the digenic architecture of congenital heart disease using trio exome sequencing data.American journal of human genetics · 2025Article
- Article
- Effect of deletion of the protein kinase PRKD1 on development of the mouse embryonic heart.Journal of anatomy · 2024Article
- Understanding the Genetic and Non-Genetic Interconnections in the Aetiology of Syndromic Congenital Heart Disease: An Updated Review: Part 2.Current cardiology reports · 2024Review
- Human Genetics of Atrioventricular Septal Defect.Advances in experimental medicine and biology · 2024Review
- Epigenomic signature of major congenital heart defects in newborns with Down syndrome.Human genomics · 2023Article
- Epigenomic signature of major congenital heart defects in newborns with Down syndrome.medRxiv : the preprint server for health sciences · 2023Article
- CRELD1 variants are associated with bicuspid aortic valve in Turner syndrome.Human genetics · 2023Article
- Article
- Genetics and Molecular Basis of Congenital Heart Defects in Down Syndrome: Role of Extracellular Matrix Regulation.International journal of molecular sciences · 2023Review
- Rare copy number variation analysis identifies disease-related variants in atrioventricular septal defect patients.Frontiers in genetics · 2023Article
- Endocardial Regulation of Cardiac Development.Journal of cardiovascular development and disease · 2022Review
- Cardiovascular physiology and pathophysiology in Down syndrome.Physiological research · 2022Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 1 country.
Funding
Abstract
About half of people with trisomy 21 have a congenital heart defect (CHD), whereas the remainder have a structurally normal heart, demonstrating that trisomy 21 is a significant risk factor but is not causal for abnormal heart development. Atrioventricular septal defects (AVSD) are the most commonly occurring heart defects in Down syndrome (DS), and ∼65% of all AVSD is associated with DS. We used a candidate-gene approach among individuals with DS and complete AVSD (cases = 141) and DS with no CHD (controls = 141) to determine whether rare genetic variants in genes involved in atrioventricular valvuloseptal morphogenesis contribute to AVSD in this sensitized population. We found a significant excess (p < 0.0001) of variants predicted to be deleterious in cases compared to controls. At the most stringent level of filtering, we found potentially damaging variants in nearly 20% of cases but fewer than 3% of controls. The variants with the highest probability of being damaging in cases only were found in six genes: COL6A1, COL6A2, CRELD1, FBLN2, FRZB, and GATA5. Several of the case-specific variants were recurrent in unrelated individuals, occurring in 10% of cases studied. No variants with an equal probability of being damaging were found in controls, demonstrating a highly specific association with AVSD. Of note, all of these genes are in the VEGF-A pathway, even though the candidate genes analyzed in this study represented numerous biochemical and developmental pathways, suggesting that rare variants in the VEGF-A pathway might contribute to the genetic underpinnings of AVSD in humans.
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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.