ArticlePloS one2011
A genetic signature of spina bifida risk from pathway-informed comprehensive gene-variant analysis.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 3 of them syntheses that pooled it.
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
21 citing papers in PubMed, 3 syntheses or guidelines pooled it, 32 citations in OpenAlex.
- MTHFD1 polymorphism as maternal risk for neural tube defects: a meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2015Pooled it
- Association between MTHFD1 G1958A polymorphism and neural tube defects susceptibility: a meta-analysis.PloS one · 2014Pooled it
- Pooled it
- Genetic variants in purine metabolism and treatment resistance in schizophrenia: evidence supporting the adenosine hypothesis - a pilot study.Frontiers in pharmacology · 2026Article
- Review
- Fundamental origins of neural tube defects with a basis in genetics and nutrition.Experimental brain research · 2025Review
- Metabolic Analysis of Methylenetetrahydrofolate Reductase Single Nucleotide Polymorphisms (MTHFR 677C<T and MTHFR 1298A<C), Serum Folate and Vitamin B12 in Neural Tube Defects.Indian journal of clinical biochemistry : IJCB · 2023Article
- Genetic mutations in ribosomal biogenesis gene TCOF1 identified in human neural tube defects.Molecular genetics & genomic medicine · 2023Article
- Article
- Association between rare variants in specific functional pathways and human neural tube defects multiple subphenotypes.Neural development · 2020Article
- Accumulation of rare coding variants in genes implicated in risk of human cleft lip with or without cleft palate.American journal of medical genetics. Part A · 2019Article
- Genetic contribution of retinoid-related genes to neural tube defects.Human mutation · 2018Article
- Mutations in folate transporter genes and risk for human myelomeningocele.American journal of medical genetics. Part A · 2017Article
- Finding the genetic mechanisms of folate deficiency and neural tube defects-Leaving no stone unturned.American journal of medical genetics. Part A · 2017Review
- DNA Methylome Profiling on the Infinium HumanMethylation450 Array from Limiting Quantities of Genomic DNA from a Single, Small Archived Bloodspot.Genetic testing and molecular biomarkers · 2017Article
- Sequence variation in folate pathway genes and risks of human cleft lip with or without cleft palate.American journal of medical genetics. Part A · 2016Article
- Observational
- Functional variant in methionine synthase reductase intron-1 is associated with pleiotropic congenital malformations.Molecular and cellular biochemistry · 2015Article
- Missing genetic risk in neural tube defects: can exome sequencing yield an insight?Birth defects research. Part A, Clinical and molecular teratology · 2014Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Despite compelling epidemiological evidence that folic acid supplements reduce the frequency of neural tube defects (NTDs) in newborns, common variant association studies with folate metabolism genes have failed to explain the majority of NTD risk. The contribution of rare alleles as well as genetic interactions within the folate pathway have not been extensively studied in the context of NTDs. Thus, we sequenced the exons in 31 folate-related genes in a 480-member NTD case-control population to identify the full spectrum of allelic variation and determine whether rare alleles or obvious genetic interactions within this pathway affect NTD risk. We constructed a pathway model, predetermined independent of the data, which grouped genes into coherent sets reflecting the distinct metabolic compartments in the folate/one-carbon pathway (purine synthesis, pyrimidine synthesis, and homocysteine recycling to methionine). By integrating multiple variants based on these groupings, we uncovered two provocative, complex genetic risk signatures. Interestingly, these signatures differed by race/ethnicity: a Hispanic risk profile pointed to alterations in purine biosynthesis, whereas that in non-Hispanic whites implicated homocysteine metabolism. In contrast, parallel analyses that focused on individual alleles, or individual genes, as the units by which to assign risk revealed no compelling associations. These results suggest that the ability to layer pathway relationships onto clinical variant data can be uniquely informative for identifying genetic risk as well as for generating mechanistic hypotheses. Furthermore, the identification of ethnic-specific risk signatures for spina bifida resonated with epidemiological data suggesting that the underlying pathogenesis may differ between Hispanic and non-Hispanic groups.
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.