Evidence map›Paper›PMID 37455310›Full record

ArticleBMC medicine2023

A functional mechanism for a non-coding variant near AGTR2 associated with risk for preterm birth.

Li Wang, Robert M Rossi, Xiaoting Chen, Jing Chen, Jilian Runyon, Mehak Chawla, Daniel Miller, Carmy Forney, Arthur Lynch, Xuzhe Zhang and 6 more

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

Article in BMC medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.6field-weighted citation impact, top 29% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. Review
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

16 authors at 2 institutions in 4 countries.

Li WangCenter for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. wanglilove2@gmail.com.ORCID 0000-0002-4460-8670
Robert M RossiCenter for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Xiaoting ChenMarch of Dimes Prematurity Research Center Ohio Collaborative, Cincinnati, OH, USA.
Jing ChenDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Jilian RunyonDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Mehak ChawlaCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Daniel MillerCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Carmy ForneyCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Arthur LynchCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Xuzhe ZhangCenter for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Fansheng KongCenter for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Bo JacobssonDepartment of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Leah C KottyanCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Matthew T WeirauchCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Ge ZhangDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Louis J MugliaCenter for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. LMuglia@bwfund.org.
Cincinnati Children's Hospital Medical Center · USNorwegian Institute of Public Health · NO

Funding

Tissue Repository CoreP30AR070549 · NIAMS · CINCINNATI CHILDRENS HOSP MED CTR · PI Grant Sanford Schulert · 2016 to 2026
$7.7M
Gene Regulation as a Foundation for Autoimmune Disease PreventionU01AI130830 · NIAID · CINCINNATI CHILDRENS HOSP MED CTR · PI WEIRAUCH, MATTHEW TYSON · 2017 to 2021
$7.2M
Harnessing "omics": A Systems Biology approach to discovery of biologicalpathways in placental development and parturitionR01HD091527 · NICHD · UNIVERSITY OF FLORIDA · PI BALONI, PRIYANKA, JONES, HELEN N · 2017 to 2021
$2.7M
Integrating genomic studies of gestational duration and birth weight to understand maternal and fetal causes of adverse pregnancy outcomes and links with later diseasesR01HD101669 · NICHD · CINCINNATI CHILDRENS HOSP MED CTR · PI FREATHY, RACHEL, JACOBSSON, BO · 2021 to 2024
$2.1M
Deletion of CRH Expression in the PlacentaR21HD090196 · NICHD · CINCINNATI CHILDRENS HOSP MED CTR · PI MUGLIA, LOUIS J, VANDEVOORT, CATHERINE A · 2017 to 2018
$443k
NIAID NIH HHS U01 AI130830NIAMS NIH HHS P30 AR070549NICHD NIH HHS R01 HD091527NICHD NIH HHS R01 HD101669NICHD NIH HHS R21 HD090196NIH HHS R01HD101669NIH HHS R21HD090196
6 · The paper itself

Abstract

backgroundPreterm birth (PTB), defined as delivery before 37 gestational weeks, imposes significant public health burdens. A recent maternal genome-wide association study of spontaneous PTB identified a noncoding locus near the angiotensin II receptor type 2 (AGTR2) gene. Genotype-Tissue Expression data revealed that alleles associated with decreased AGTR2 expression in the uterus were linked to an increased risk of PTB and shortened gestational duration. We hypothesized that a causative variant in this locus modifies AGTR2 expression by altering transcription factor (TF) binding.

methodsTo investigate this hypothesis, we performed bioinformatics analyses and functional characterizations at the implicated locus. Potential causal single nucleotide polymorphisms (SNPs) were prioritized, and allele-dependent binding of TFs was predicted. Reporter assays were employed to assess the enhancer activity of the top PTB-associated non-coding variant, rs7889204, and its impact on TF binding.

resultsOur analyses revealed that rs7889204, a top PTB-associated non-coding genetic variant is one of the strongest eQTLs for the AGTR2 gene in uterine tissue samples. We observed differential binding of CEBPB (CCAAT enhancer binding protein beta) and HOXA10 (homeobox A10) to the alleles of rs7889204. Reporter assays demonstrated decreased enhancer activity for the rs7889204 risk "C" allele.

conclusionCollectively, these results demonstrate that decreased AGTR2 expression caused by reduced transcription factor binding increases the risk for PTB and suggest that enhancing AGTR2 activity may be a preventative measure in reducing PTB risk.

Indexed as

Premature BirthFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInfant, NewbornPolymorphism, Single NucleotideTranscription FactorsTranscription FactorsAGTR2Functional studiesNon-coding variantPreterm birth

Identifiers

PMID37455310
PMCPMC10351137
OpenAlexW4384465850

What OpenQuestion holds

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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.