Evidence map›Paper›PMID 31851787›Full record

ArticleMolecular genetics & genomic medicine2020

Gene-by-gene interactions associated with the risk of conotruncal heart defects.

Chen Lyu, Daniel M Webber, Stewart L MacLeod, Charlotte A Hobbs, Ming Li, National Birth Defects Prevention Study

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular genetics & genomic medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.3field-weighted citation impact, top 39% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 8 citations in OpenAlex.

  1. Prenatal diagnosis and clinical pregnancy outcome of fetuses with conotruncal defects in a Chinese cohort.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 1 country.

Chen LyuDepartment of Epidemiology and Biostatistics, Indiana University, Bloomington, IN, USA.
Daniel M WebberDepartment of Pathology & Immunology, Washington University at St Louis, Saint Louis, MO, USA.
Stewart L MacLeodArkansas Children's Research Institute, Little Rock, AR, USA.
Charlotte A HobbsRady Children's Institute for Genomic Medicine, San Diego, CA, USA.
Ming LiDepartment of Epidemiology and Biostatistics, Indiana University, Bloomington, IN, USA.ORCID 0000-0003-0273-6217
National Birth Defects Prevention Study
Indiana University Bloomington · USArkansas Children's Hospital · USChildren’s Institute · USWashington University in St. Louis · US

Funding

Random Field Modelling of genetic and epigenetic association underlying congenital heart defects in the presence of disease heterogeneityK01HL140333 · NHLBI · TRUSTEES OF INDIANA UNIVERSITY · PI LI, MING · 2018 to 2021
$724k
Gene-by-Gene and Gene-by-Environment Interactions Underlying Congenital Heart DefectsR03HD092854 · NICHD · TRUSTEES OF INDIANA UNIVERSITY · PI LI, MING · 2018 to 2019
$171k
NHLBI NIH HHS K01 HL140333NICHD NIH HHS R03 HD092854
6 · The paper itself

Abstract

backgroundThe development of conotruncal heart defects (CTDs) involves a complex relationship among genetic variants and maternal lifestyle factors. In this article, we focused on the interactions between 13 candidate genes within folate, homocysteine, and transsulfuration pathways for potential association with CTD risk.

methodsTargeted sequencing was used for 328 case-parental triads enrolled in the National Birth Defects Prevention Study (NBDPS). To evaluate the interaction of two genes, we applied a conditional logistic regression model for all possible SNP pairs within two respective genes by contrasting the affected infants with their pseudo-controls. The findings were replicated in an independent sample of 86 NBDPS case-parental triads genotyped by DNA microarrays. The results of two studies were further integrated by a fixed-effect meta-analysis.

resultsOne SNP pair (i.e., rs4764267 and rs6556883) located in gene MGST1 and GLRX, respectively, was found to be associated with CTD risk after multiple testing adjustment using simpleM, a modified Bonferroni correction approach (nominal p-value of 4.62e-06; adjusted p-value of .04). Another SNP pair (i.e., rs11892646 and rs56219526) located in gene DNMT3A and MTRR, respectively, achieved marginal significance after multiple testing adjustment (adjusted p-value of .06).

conclusionFurther studies with larger sample sizes are needed to confirm and elucidate these potential interactions.

Indexed as

Epistasis, GeneticPolymorphism, Single NucleotideDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3AFerredoxin-NADP ReductaseGlutaredoxinsGlutathione TransferaseHeart Defects, CongenitalHumansPedigreeDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNMT3A protein, humanFerredoxin-NADP ReductaseGLRX protein, humanGlutaredoxinsGlutathione Transferasemethionine synthase reductasemicrosomal glutathione S-transferase-Icase-parental triadsconditional logistic regressionconotroncal heart defectsgene-by-gene interactionmeta-analysissingle nucleotide polymorphism

Identifiers

PMID31851787
PMCPMC6978401
OpenAlexW2994881477

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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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.