Evidence map›Paper›PMID 39332409›Full record

ArticleAmerican journal of human genetics2024

Common variants increase risk for congenital diaphragmatic hernia within the context of de novo variants.

Lu Qiao, Carrie L Welch, Rebecca Hernan, Julia Wynn, Usha S Krishnan, Jill M Zalieckas, Terry Buchmiller, Julie Khlevner, Aliva De, Christiana Farkouh-Karoleski and 41 more

Abstract read
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In one paragraph

Article in American journal of human genetics, 2024. 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
–field-weighted citation impact
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.

  1. Review
  2. Mechanical compression causes lung hypoplasia in congenital diaphragmatic hernia with GATA4 genetic variants.American journal of physiology. Lung cellular and molecular physiology · 2026
    Article
  3. Review
  4. Article
  5. Article
  6. Modeling patient variants ofbioRxiv : the preprint server for biology · 2026
    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

51 authors.

Lu QiaoDepartment of Pediatrics, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Carrie L WelchDepartment of Pediatrics, Columbia University Irving Medical Center, New York, NY 10032, USA.
Rebecca HernanDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Julia WynnDepartment of Pediatrics, Columbia University Irving Medical Center, New York, NY 10032, USA.
Usha S KrishnanDepartment of Pediatrics, Columbia University Irving Medical Center, New York, NY 10032, USA.
Jill M ZalieckasDepartment of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Anesthesiology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Terry BuchmillerDepartment of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Julie KhlevnerDepartment of Pediatrics, Columbia University Irving Medical Center, New York, NY 10032, USA.
Aliva DeDepartment of Pediatrics, Columbia University Irving Medical Center, New York, NY 10032, USA.
Christiana Farkouh-KaroleskiDepartment of Pediatrics, Columbia University Irving Medical Center, New York, NY 10032, USA.
Amy J WagnerChildren's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Andreas HeydweillerDepartment of General, Visceral, Vascular, and Thoracic Surgery, Unit of Pediatric Surgery, University Hospital Bonn, Bonn, Germany.
Andreas C MuellerDepartment of Neonatology and Pediatric Intensive Care, Children's Hospital, University of Bonn, Bonn, Germany.
Annelies de KleinDepartment of Clinical Genetics, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands.
Brad W WarnerWashington University School of Medicine, St. Louis, MO 63110, USA.
Carlo MajInstitute for Genomic Statistics and Bioinformatics, University of Bonn, Bonn, Germany.
Dai ChungMonroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, TN 37232, USA.
David J McCulleyDepartment of Pediatrics, San Diego Medical School, University of California, San Diego, San Diego, CA 92092, USA.
David SchindelMedical City Children's Hospital, Dallas, TX 75230, USA.
Douglas PotokaUniversity of Pittsburgh, Pittsburgh, PA 15224, USA.
Elizabeth FialkowskiOregon Health and Science University, Portland, OR 97239, USA.
Felicitas SchulzDepartment of Hematology, Oncology and Clinical Immunology, University Hospital Düsseldorf, Düsseldorf, Germany.
Florian KipfmullerDepartment of Neonatology and Pediatric Intensive Care, Children's Hospital, University of Bonn, Bonn, Germany.
Foong-Yen LimCincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Frank MagielsenDepartment of Clinical Genetics, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands.
George B MychaliskaUniversity of Michigan Health System, Ann Arbor, MI 48109, USA.
Gudrun AspelundDepartment of Pediatrics, Columbia University Irving Medical Center, New York, NY 10032, USA.
Heiko Martin ReutterNeonatology and Pediatric Intensive Care, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Erlangen, Germany.
Howard NeedelmanUniversity of Nebraska Medical Center College of Medicine, Omaha, NE 68114, USA.
J Marco SchnaterDepartment of Pediatric Surgery, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands.
Jason C FisherNew York University Grossman School of Medicine, Hassenfeld Children's Hospital at NYU Langone, New York, NY 10016, USA.
Kenneth AzarowOregon Health and Science University, Portland, OR 97239, USA.
Mahmoud ElfikyCairo University, Cairo 11432, Egypt.
Markus M NöthenInstitute of Human Genetics, University of Bonn, Bonn, Germany.
Melissa E DankoMonroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, TN 37232, USA.
Mindy LiRush University Medical Center, Chicago, IL 60612, USA.
Przemyslaw KosińskiDepartment of Obstetrics, Perinatology and Gynecology, Medical University of Warsaw, 02-091 Warsaw, Poland.
Rene M H WijnenDepartment of Pediatric Surgery, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands.
Robert A CusickUniversity of Nebraska Medical Center College of Medicine, Omaha, NE 68114, USA.
Samuel Z SofferNorthwell Health, New York, NY 11040, USA.
Suzan C M Cochius-Den OtterDepartment of Neonatology and Pediatric Intensive Care, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands.
Thomas SchaibleDepartment of Neonatology, University Children's Hospital Mannheim, University of Heidelberg, Mannheim, Germany.
Timothy CrombleholmeMedical City Children's Hospital, Dallas, TX 75230, USA.
Vincent P DuronDepartment of Surgery (Pediatrics), Columbia University Irving Medical Center, New York, NY 10032, USA.
Patricia K DonahoePediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Surgery, Harvard Medical School, Boston, MA 02115, USA.
Xin SunDepartment of Pediatrics, San Diego Medical School, University of California, San Diego, San Diego, CA 92092, USA.
Frances A HighDepartment of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA.
Charlotte BendixenDepartment of General, Visceral, Vascular, and Thoracic Surgery, Unit of Pediatric Surgery, University Hospital Bonn, Bonn, Germany.
Erwin BrosensDepartment of Clinical Genetics, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands.
Yufeng ShenDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY 10032, USA; JP Sulzberger Columbia Genome Center, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address: ys2411@cumc.columbia.edu.
Wendy K ChungDepartment of Pediatrics, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: wendy.chung@childrens.harvard.edu.

Funding

CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR024156 · NCRR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2006 to 2011
$53.0M
THE DROSOPHILA GENETICS AND RNAI CORE (THE FLY CORE)P01HD068250 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI CHUNG, WENDY K, DONAHOE, PATRICIA K · 2011 to 2022
$17.1M
Identification of Novel Genes for Congenital Diaphragmatic HerniaR01HD057036 · NICHD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ASPELUND, GUDRUN, CHUNG, WENDY K · 2008 to 2012
$2.8M
GENETIC AND DEVELOPMENTAL MECHANISMS OF CONGENITAL DIAPHRAGMATIC HERNIAR01HL146859 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI MCCULLEY, DAVID J · 2019 to 2023
$2.0M
Integrate cancer genomics data in geneticstudies and diagnosis of developmental disordersR01GM120609 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SHEN, YUFENG · 2017 to 2021
$1.7M
Computational methods to interpret genomic variation and integrate functional genomics data in genetic analysis of human diseasesR35GM149527 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Yufeng Shen · 2023 to 2026
$1.6M
Genetic analysis of structural birth defects by integration of multiple diseases with epigenomic data and cancer mutationsR03HL138352 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SHEN, YUFENG · 2017 to 2018
$320k
Computational analysis of whole genome sequence data for discovering novel risk genes of structural birth defectsR03HL161595 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SHEN, YUFENG · 2022 to 2023
$319k
NCRR NIH HHS UL1 RR024156NHLBI NIH HHS R01 HL146859NHLBI NIH HHS R03 HL138352NHLBI NIH HHS R03 HL161595NICHD NIH HHS P01 HD068250NICHD NIH HHS R01 HD057036NIGMS NIH HHS R01 GM120609NIGMS NIH HHS R35 GM149527
6 · The paper itself

Abstract

Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly often accompanied by other structural anomalies and/or neurobehavioral manifestations. Rare de novo protein-coding variants and copy-number variations contribute to CDH in the population. However, most individuals with CDH remain genetically undiagnosed. Here, we perform integrated de novo and common-variant analyses using 1,469 CDH individuals, including 1,064 child-parent trios and 6,133 ancestry-matched, unaffected controls for the genome-wide association study. We identify candidate CDH variants in 15 genes, including eight novel genes, through deleterious de novo variants. We further identify two genomic loci contributing to CDH risk through common variants with similar effect sizes among Europeans and Latinx. Both loci are in putative transcriptional regulatory regions of developmental patterning genes. Estimated heritability in common variants is ∼19%. Strikingly, there is no significant difference in estimated polygenic risk scores between isolated and complex CDH or between individuals harboring deleterious de novo variants and individuals without these variants. The data support a polygenic model as part of the CDH genetic architecture.

Indexed as

Genetic Predisposition to DiseaseGenome-Wide Association StudyHernias, Diaphragmatic, CongenitalCase-Control StudiesDNA Copy Number VariationsFemaleGenetic VariationHumansMaleMultifactorial InheritancePolymorphism, Single NucleotideRisk Factorscommon variantscongenital diaphragmatic herniade novo variantsgenome-wide association studysingle-nucleotide polymorphismWNT5A

Identifiers

PMID39332409
PMCPMC11568762

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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.