Evidence map›Paper›PMID 37026454›Full record

SynthesisCirculation. Genomic and precision medicine2023

Oligogenic Architecture of Rare Noncoding Variants Distinguishes 4 Congenital Heart Disease Phenotypes.

Mengyao Yu, Matthew Aguirre, Meiwen Jia, Ketrin Gjoni, Aldo Cordova-Palomera, Chad Munger, Dulguun Amgalan, X Rosa Ma, Alexandre Pereira, Catherine Tcheandjieu and 18 more

Open access · bronzeAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Circulation. Genomic and precision medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

8 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Genetics of Congenital Heart Disease.Clinics in perinatology · 2025
    Review
  5. Article
  6. Article
  7. Article
  8. Article
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

28 authors at 16 institutions in 5 countries.

Mengyao YuDepartment of Pediatrics (M.Y., M.A., A.C.-P., C.T., J.R.P.), Stanford University School of Medicine.ORCID 0000-0002-5346-535X
Matthew AguirreDepartment of Pediatrics (M.Y., M.A., A.C.-P., C.T., J.R.P.), Stanford University School of Medicine.
Meiwen JiaDepartment of Translational Research in Psychiatry, Max Planck Institute of Psychiatry Munich, Germany (M.J., B.M.-M.).
Ketrin GjoniGladstone Institutes; University of California San Francisco (K.G., C.T., D.S., K.S.P.).ORCID 0000-0001-5833-1089
Aldo Cordova-PalomeraDepartment of Pediatrics (M.Y., M.A., A.C.-P., C.T., J.R.P.), Stanford University School of Medicine.
Chad MungerDepartment of Genetics (C.M., D.A., X.R.M., J.M.E.), Stanford University School of Medicine.ORCID 0000-0003-1906-1164
Dulguun AmgalanDepartment of Genetics (C.M., D.A., X.R.M., J.M.E.), Stanford University School of Medicine.ORCID 0000-0001-6398-3372
X Rosa MaDepartment of Genetics (C.M., D.A., X.R.M., J.M.E.), Stanford University School of Medicine.ORCID 0000-0001-8297-4279
Alexandre PereiraDepartment of Genetics, Harvard University, Cambridge, MA (A.P., C.S., J.S.).ORCID 0000-0002-7782-5540
Catherine TcheandjieuDepartment of Pediatrics (M.Y., M.A., A.C.-P., C.T., J.R.P.), Stanford University School of Medicine.ORCID 0000-0001-9559-4339
Christine SeidmanDepartment of Genetics, Harvard University, Cambridge, MA (A.P., C.S., J.S.).ORCID 0000-0001-6380-1209
Jonathan SeidmanDepartment of Genetics, Harvard University, Cambridge, MA (A.P., C.S., J.S.).ORCID 0000-0002-9082-3566
Martin Tristani-FirouziDepartment of Pediatrics, University of Utah, Salt Lake City (M.T.-F.).ORCID 0000-0001-5916-442X
Wendy ChungDepartment of Pediatrics, Columbia University, NY (W.C.).ORCID 0000-0003-3438-5685
Elizabeth GoldmuntzDepartment of Pediatrics, University of Pennsylvania, Philadelphia (E.G.).ORCID 0000-0003-2936-4396
Deepak SrivastavaGladstone Institutes; University of California San Francisco (K.G., C.T., D.S., K.S.P.).ORCID 0000-0002-3480-5953
Ruth J F LoosIcahn School of Medicine at Mount Sinai, NY (R.J.F.L., N.C.).ORCID 0000-0002-8532-5087
Nathalie ChamiIcahn School of Medicine at Mount Sinai, NY (R.J.F.L., N.C.).ORCID 0000-0002-8547-6424
Heather CordellPopulation Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne, United Kingdom (H.C.).ORCID 0000-0002-1879-5572
Martina DreßenDepartment of Cardiovascular Surgery, Division of Experimental Surgery, Institute Insure (Institute for Translational Cardiac Surgery), German Heart Center Munich & Technical University of Munich, School of Medicine & Health, Germany (M.D., H.L., M.K.).
Bertram Mueller-MyhsokDepartment of Translational Research in Psychiatry, Max Planck Institute of Psychiatry Munich, Germany (M.J., B.M.-M.).
Harald LahmDepartment of Cardiovascular Surgery, Division of Experimental Surgery, Institute Insure (Institute for Translational Cardiac Surgery), German Heart Center Munich & Technical University of Munich, School of Medicine & Health, Germany (M.D., H.L., M.K.).ORCID 0000-0002-4477-3406
Markus KraneDepartment of Cardiovascular Surgery, Division of Experimental Surgery, Institute Insure (Institute for Translational Cardiac Surgery), German Heart Center Munich & Technical University of Munich, School of Medicine & Health, Germany (M.D., H.L., M.K.).
Katherine S PollardGladstone Institutes; University of California San Francisco (K.G., C.T., D.S., K.S.P.).ORCID 0000-0002-9870-6196
Jesse M EngreitzDepartment of Genetics (C.M., D.A., X.R.M., J.M.E.), Stanford University School of Medicine.
Sarah A Gagliano TaliunDepartment of Medicine & Department of Neurosciences, Faculty of Medicine, University ersité de Montréal (S.A.G.T.).ORCID 0000-0003-1306-1868
Bruce D GelbThe Mindich Child Health & Development Institute at the Hess Center for Science & Medicine at Mount Sinai, NY (B.D.G.).ORCID 0000-0001-8527-5027
James R PriestDepartment of Pediatrics (M.Y., M.A., A.C.-P., C.T., J.R.P.), Stanford University School of Medicine.ORCID 0000-0002-2505-617X
Stanford University · USGladstone Institutes · USDeutsches Herzzentrum München · DEHarvard University Press · USIcahn School of Medicine at Mount Sinai · USMax Planck Institute of Psychiatry · DECentre for Life · GBChild Health and Development Institute · USColumbia University Irving Medical Center · USElizabeth City State University · USFudan University · CNHarvard University · USLucile Packard Children's Hospital · USMontreal Heart Institute · CAUniversity of Utah · USYale New Haven Hospital · US

Funding

Administrative Coordinating Center: Cardiovascular Development and Pediatric Cardiac Genomics ConsortiaU01HL131003 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI CNOTA, JAMES, OLLBERDING, NICHOLAS J · 2016 to 2024
$54.8M
Genomic Effects on Right Ventricular Function, Clinical Features and Outcomes in CHDU01HL098147 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI NEWBURGER, JANE W., ROBERTS, AMY E · 2009 to 2024
$6.7M
Genetic determinants of human heterotaxy and aortic arch malformationU01HL098162 · NHLBI · YALE UNIVERSITY · PI BRUECKNER, MARTINA, GRUBER, PETER J · 2009 to 2024
$5.9M
The Genetic Basis of Conotruncal DefectsU01HL098153 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI GOLDMUNTZ, ELIZABETH · 2009 to 2014
$4.3M
Molecular approaches to gene identification in congenital heart diseaseU01HL098163 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CHUNG, WENDY K, WARBURTON, DOROTHY P. · 2009 to 2014
$3.9M
Genetics of Hypoplastic Left Heart SyndromeUM1HL128761 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI BERNSTEIN, DANIEL, SRIVASTAVA, DEEPAK · 2015 to 2019
$2.5M
The Genomic Basis of Congenital Heart Disease and Neurodevelopmental OutcomesUM1HL098147 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI NEWBURGER, JANE W., ROBERTS, AMY E · 2015 to 2019
$2.4M
Genetics of conotruncal defects and associated neurodevelopmental outcomesUM1HL098123 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI GELB, BRUCE D · 2015 to 2019
$2.3M
Genetics and genomics of congenital heart disease and associated neurodevelopmental abnormalitiesUM1HL098162 · NHLBI · YALE UNIVERSITY · PI BRUECKNER, MARTINA, GUPTA, ABHA RANI · 2015 to 2019
$2.2M
Bridging the Gap between Genomics and Clinical Outcomes in CHDU01HL128711 · NHLBI · UNIVERSITY OF UTAH · PI TRISTANI-FIROUZI, MARTIN, YANDELL, MARK DOUGLAS · 2020 to 2024
$2.1M
Bridging the Gap between Genomics and Clinical Outcomes in CHDUM1HL128711 · NHLBI · UNIVERSITY OF UTAH · PI TRISTANI-FIROUZI, MARTIN, YANDELL, MARK DOUGLAS · 2015 to 2019
$2.0M
Pediatric Heart Network Joint Heart Program ConsortiumUM1HL172717 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI Louis Bezold, James Cnota · 2024 to 2026
$1.3M
NHLBI NIH HHS K99 HL130523NHLBI NIH HHS R00 HL130523NHLBI NIH HHS U01 HL098147NHLBI NIH HHS U01 HL098153NHLBI NIH HHS U01 HL098162NHLBI NIH HHS U01 HL098163NHLBI NIH HHS U01 HL128711NHLBI NIH HHS U01 HL131003NHLBI NIH HHS UM1 HL098123NHLBI NIH HHS UM1 HL098147NHLBI NIH HHS UM1 HL098162NHLBI NIH HHS UM1 HL128711NHLBI NIH HHS UM1 HL128761NHLBI NIH HHS UM1 HL172717
6 · The paper itself

Abstract

backgroundCongenital heart disease (CHD) is highly heritable, but the power to identify inherited risk has been limited to analyses of common variants in small cohorts.

methodsWe performed reimputation of 4 CHD cohorts (n=55 342) to the TOPMed reference panel (freeze 5), permitting meta-analysis of 14 784 017 variants including 6 035 962 rare variants of high imputation quality as validated by whole genome sequencing.

resultsMeta-analysis identified 16 novel loci, including 12 rare variants, which displayed moderate or large effect sizes (median odds ratio, 3.02) for 4 separate CHD categories. Analyses of chromatin structure link 13 of the genome-wide significant loci to key genes in cardiac development; rs373447426 (minor allele frequency, 0.003 [odds ratio, 3.37 for Conotruncal heart disease];

conclusionsWe describe a set of rare noncoding variants conferring significant risk for individual heart malformations which are linked to genes governing cardiac development. These results illustrate that the oligogenic basis of CHD and significant heritability may be linked to rare variants outside protein-coding regions conferring substantial risk for individual categories of cardiac malformation.

Indexed as

Heart Defects, CongenitalAdaptor Proteins, Signal TransducingChromatinGene FrequencyHumansPhenotypeWhole Genome SequencingAdaptor Proteins, Signal TransducingChromatinSPAG9 protein, humanalleleschromatinlive birthphenotypeprevalence

Identifiers

PMID37026454
PMCPMC10330096
OpenAlexW4362692986

What OpenQuestion holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

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.