ArticleCirculation. Cardiovascular genetics2012
Complex trait analysis of ventricular septal defects caused by Nkx2-5 mutation.
Article in Circulation. Cardiovascular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 33 citations in OpenAlex.
- A novel GDF1 frameshift mutation in a young adult with right coronary artery hypoplasia and myocardial bridging: a case report.Frontiers in cardiovascular medicine · 2026Article
- Genetic impact of copy number variations on congenital heart defects: Current insights and future directions.Global medical genetics · 2025Review
- Human Genetics of Congenital Heart Defects.Advances in experimental medicine and biology · 2024Review
- Molecular Pathways and Animal Models of Ebstein's Anomaly.Advances in experimental medicine and biology · 2024Review
- Genetic studies in the Pakistani population reveal novel associations with ventricular septal defects (VSDs).BMC pediatrics · 2023Article
- Article
- Fetal Congenital Heart Disease Caused by Compound Heterozygous Mutations in theFrontiers in genetics · 2021Article
- Axenfeld-Rieger syndrome-associated mutants of the transcription factor FOXC1 abnormally regulateThe Journal of biological chemistry · 2020Article
- Genetic Basis for Congenital Heart Disease: Revisited: A Scientific Statement From the American Heart Association.Circulation · 2018Review
- Role of Segregation for Variant Discovery in Multiplex Families Ascertained by Probands With Left Sided Cardiovascular Malformations.Frontiers in genetics · 2018Article
- Atrial ERK1/2 activation in the embryo leads to incomplete Septal closure: a novel mouse model of atrial Septal defect.Journal of biomedical science · 2017Article
- The Complex Genetic Basis of Congenital Heart Defects.Circulation journal : official journal of the Japanese Circulation Society · 2017Review
- Nkx2-5 and Sarcospan genetically interact in the development of the muscular ventricular septum of the heart.Scientific reports · 2017Article
- Point mutations in murineJCI insight · 2017Article
- Genetics and Genomics of Congenital Heart Disease.Circulation research · 2017Review
- Gerbode Ventricular Septal Defect -A Rare Cardiac Anomaly Associated with Genetic Variants in Indian Population- A Case Series.Journal of clinical and diagnostic research : JCDR · 2017Article
- Inhibition of Gata4 and Tbx5 by Nicotine-Mediated DNA Methylation in Myocardial Differentiation.Stem cell reports · 2017Article
- Transgenerational cardiology: One way to a baby's heart is through the mother.Molecular and cellular endocrinology · 2016Review
- The importance of copy number variation in congenital heart disease.NPJ genomic medicine · 2016Article
- Pax8 plays a pivotal role in regulation of cardiomyocyte growth and senescence.Journal of cellular and molecular medicine · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundThe occurrence of a congenital heart defect has long been thought to have a multifactorial basis, but the evidence is indirect. Complex trait analysis could provide a more nuanced understanding of congenital heart disease. METHODS AND
resultsWe assessed the role of genetic and environmental factors on the incidence of ventricular septal defects (VSDs) caused by a heterozygous Nkx2-5 knockout mutation. We phenotyped >3100 hearts from a second-generation intercross of the inbred mouse strains C57BL/6 and FVB/N. Genetic linkage analysis mapped loci with lod scores of 5 to 7 on chromosomes 6, 8, and 10 that influence the susceptibility to membranous VSDs in Nkx2-5(+/-) animals. The chromosome 6 locus overlaps one for muscular VSD susceptibility. Multiple logistic regression analysis for environmental variables revealed that maternal age is correlated with the risk of membranous and muscular VSD in Nkx2-5(+/-) but not wild-type animals. The maternal age effect is unrelated to aneuploidy or a genetic polymorphism in the affected individuals. The risk of a VSD is not only complex but dynamic. Whereas the effect of genetic modifiers on risk remains constant, the effect of maternal aging increases over time.
conclusionsEnumerable factors contribute to the presentation of a congenital heart defect. The factors that modify rather than cause congenital heart disease substantially affect risk in predisposed individuals. Their characterization in a mouse model offers the potential to narrow the search space in human studies and to develop alternative strategies for prevention.
Indexed as
Identifiers
What OpenQuestion holds
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.