ArticleNature genetics2017
Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands.
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In one paragraph
Article in Nature genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 552 papers, 4 of them syntheses that pooled it.
0numbers the graph read from it
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552citing papers in PubMed, 4 pooled it
30.2field-weighted citation impact, top 1% of its field
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Who cites it
552 citing papers in PubMed, 4 syntheses or guidelines pooled it, 913 citations in OpenAlex.
- Genetics in Heterotaxy: A Case Series and Literature Review on DNAH9, PKD1L1, MMP21, and GDF1.Clinical genetics · 2026Pooled it
- Genome-wide association studies highlight novel risk loci for septal defects and left-sided congenital heart defects.BMC genomics · 2024Pooled it
- Meta-analysis of 46,000 germline de novo mutations linked to human inherited disease.Human genomics · 2024Pooled it
- Single-cell reconstruction and mutation enrichment analysis identifies dysregulated cardiomyocyte and endothelial cells in congenital heart disease.Physiological genomics · 2023Pooled it
- Engineered human induced pluripotent stem cell models reveal altered podocytogenesis in congenital heart disease-associated SMAD2 mutations.Nature biomedical engineering · 2026Article
- A Spatiotemporal Single-Cell Atlas Uncovers Dysregulated ECM Dynamics and Septal Remodeling Arrest in Human Ventricular Septal Defects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cardiac Organoids for Modeling Congenital Heart Disease: From Genetic Discovery to Therapeutic Screening.Current cardiology reports · 2026Review
- Functional genomics iniScience · 2026Article
- Delayed Diagnosis of Congenital Heart Diseases in Adults: Opportunities for Improving Diagnostic Strategies.Journal of cardiovascular development and disease · 2026Review
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- Congenital heart defects: familial recurrence patterns in Sweden.European heart journal · 2026Article
- MYH6 in Congenital Heart Defects: A Genotype-Phenotype Characterization in a French Cohort.Pediatric cardiology · 2026Article
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- Uniparental Disomy Reveals Hidden Genetic Causes of Congenital Heart Disease.Research square · 2026Article
- CDK1 and CEP97 cooperatively control centriole length to orchestrate ciliogenesis and developmental patterning.Genes & development · 2026Article
- Body Region Dysmorphology Is Predictive of Genetic Diagnoses in Infants With Congenital Heart Disease.Molecular genetics & genomic medicine · 2026Article
- Identification of mitochondrial energy metabolism-related candidate genes UQCR10 and NDUFA6 in pediatric tetralogy of fallot: an exploratory bioinformatics study.Journal of cardiothoracic surgery · 2026Article
- Inference of elevated mutation rates and variant effects using 700k exomes.bioRxiv : the preprint server for biology · 2026Article
- Assessing the contribution of rare variants to congenital heart disease through a large-scale case-control exome study.NPJ genomic medicine · 2026Article
- Roles of ER Membrane Protein Complex in Protein Biogenesis and Quality Control in the Lung and Beyond.Cell proliferation · 2026Review
492 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
45 authors at 20 institutions in 3 countries.
Sheng Chih JinDepartment of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.
Jason HomsyDepartment of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
Samir ZaidiDepartment of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.
Qiongshi LuDepartment of Biostatistics, Yale School of Public Health, New Haven, Connecticut, USA.ORCID http://orcid.org/0000-0002-4514-0969
Sarah MortonDivision of Newborn Medicine, Department of Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.
Steven R DePalmaDepartment of Genetics, Harvard Medical School, Boston, Massachusetts, USA.ORCID http://orcid.org/0000-0002-0381-5016
Xue ZengDepartment of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.
Hongjian QiDepartment of Applied Physics and Applied Mathematics, Columbia University, New York, New York, USA.
Weni ChangDepartment of Pediatrics, Columbia University Medical Center, New York, New York, USA.
Michael C SierantDepartment of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.
Wei-Chien HungDepartment of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.
Shozeb HaiderDepartment of Computational Chemistry, University College London School of Pharmacy, London, UK.ORCID http://orcid.org/0000-0003-2650-2925
Junhui ZhangDepartment of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.
James KnightYale Center for Genome Analysis, Yale University, New Haven, Connecticut, USA.ORCID http://orcid.org/0000-0003-1166-0437
Robert D BjornsonYale Center for Genome Analysis, Yale University, New Haven, Connecticut, USA.
Christopher CastaldiYale Center for Genome Analysis, Yale University, New Haven, Connecticut, USA.
Irina R TikhonoaYale Center for Genome Analysis, Yale University, New Haven, Connecticut, USA.
Kaya BilguvarYale Center for Genome Analysis, Yale University, New Haven, Connecticut, USA.
Shrikant M ManeYale Center for Genome Analysis, Yale University, New Haven, Connecticut, USA.
Stephan J SandersDepartment of Psychiatry, University of California San Francisco, San Francisco, California, USA.
Seema MitalDepartment of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0002-7643-4484
Mark W RussellDivision of Pediatric Cardiology, University of Michigan, Ann Arbor, Michigan, USA.
J William GaynorDepartment of Pediatric Cardiac Surgery, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
John DeanfieldDepartment of Cardiology, University College London and Great Ormond Street Hospital, London, UK.
Alessandro GiardiniDepartment of Cardiology, University College London and Great Ormond Street Hospital, London, UK.
George A PorterDepartment of Pediatrics, University of Rochester Medical Center, The School of Medicine and Dentistry, Rochester, New York, USA.ORCID http://orcid.org/0000-0003-0726-9988
Deepak SrivastavaGladstone Institute of Cardiovascular Disease, San Francisco, California, USA.
Cecelia W LoDepartment of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.ORCID http://orcid.org/0000-0003-4314-3434
Yufeng ShenDepartments of Systems Biology and Biomedical Informatics, Columbia University Medical Center, New York, New York, USA.
W Scott WatkinsDepartment of Human Genetics, Eccles Institute of Human Genetics, University of Utah and School of Medicine, Salt Lake City, Utah, USA.
Mark YandellDepartment of Human Genetics, Eccles Institute of Human Genetics, University of Utah and School of Medicine, Salt Lake City, Utah, USA.
H Joseph YostDepartment of Human Genetics, Eccles Institute of Human Genetics, University of Utah and School of Medicine, Salt Lake City, Utah, USA.
Martin Tristani-FirouziDivision of Pediatric Cardiology, University of Utah, Salt Lake City, Utah, USA.
Jane W NewburgerDepartment of Cardiology, Boston Children's Hospital, Boston, Massachusetts, USA.
Amy E RobertsDepartment of Cardiology, Boston Children's Hospital, Boston, Massachusetts, USA.
Richard KimPediatric Cardiac Surgery, Children's Hospital of Los Angeles, Los Angeles, California, USA.
Hongyu ZhaoDepartment of Biostatistics, Yale School of Public Health, New Haven, Connecticut, USA.
Jonathan R KaltmanHeart Development and Structural Diseases Branch, Division of Cardiovascular Sciences, NHLBI/NIH, Bethesda, Maryland, USA.
Elizabeth GoldmuntzDepartment of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Wendy K ChungDepartments of Pediatrics and Medicine, Columbia University Medical Center, New York, New York, USA.
Jonathan G SeidmanDepartment of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
Bruce D GelbMindich Child Health and Development Institute and Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York, USA.ORCID http://orcid.org/0000-0001-8527-5027
Christine E SeidmanDepartment of Genetics, Harvard Medical School, Boston, Massachusetts, USA.ORCID http://orcid.org/0000-0001-6380-1209
Richard P LiftonDepartment of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.
Martina BruecknerDepartment of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.ORCID http://orcid.org/0000-0003-0347-5389
Yale University · USUniversity of Utah · USBoston Children's Hospital · USColumbia University Irving Medical Center · USBrigham and Women's Hospital · USGreat Ormond Street Hospital · GBHarvard University · USChild Health and Development Institute · USChildren's Hospital of Los Angeles · USChildren's Hospital of Philadelphia · USColumbia University · USGladstone Institutes · USNational Heart Lung and Blood Institute · USUniversity College London · GBUniversity of California, San Francisco · USUniversity of Michigan · USUniversity of Pennsylvania · USUniversity of Pittsburgh · USUniversity of Rochester Medical Center · USUniversity of Toronto · CA
Funding
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MAdministrative Coordinating Center: Cardiovascular Development and Pediatric Cardiac Genomics ConsortiaU01HL131003 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI CNOTA, JAMES, OLLBERDING, NICHOLAS J · 2016 to 2024
$54.8MMEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9MNHLBI Pediatric Translational Consortium Administrative Coordinating CenterU01HL098188 · NHLBI · NEW ENGLAND RESEARCH INSTITUTES, INC. · PI HAMZA, TAYE, MILLER, JULIE ELAINE · 2009 to 2015
$41.3MInstitutional Clinical and Translational Science AwardUL1TR000003 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2012 to 2015
$38.9MUniversity of Utah Center for Clinical and Translational ScienceUL1TR001067 · NCATS · UNIVERSITY OF UTAH · PI DERE, WILLARD H., HESS, RACHEL · 2013 to 2017
$19.8MYale Center for Mendelian DisordersU54HG006504 · NHGRI · YALE UNIVERSITY · PI GERSTEIN, MARK BENDER, GUNEL, MURAT · 2012 to 2015
$11.0MModeling the genetic basis for human congenital heart disease in miceU01HL098180 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LO, CECILIA W. · 2009 to 2014
$8.5MGENETICS AND GENOMICS OF HUMAN DISEASET32HD007149 · NICHD · YALE UNIVERSITY · PI James P Noonan · 1985 to 2026
$8.2MGenome-wide Analysis of Cardiac Development in ZebrafishU01HL098160 · NHLBI · UNIVERSITY OF UTAH · PI YOST, H. JOSEPH · 2009 to 2014
$8.0MGenomic 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
$6.7MGenetic determinants of human heterotaxy and aortic arch malformationU01HL098162 · NHLBI · YALE UNIVERSITY · PI BRUECKNER, MARTINA, GRUBER, PETER J · 2009 to 2024
$5.9MNCATS NIH HHS UL1 TR000003NCATS NIH HHS UL1 TR001067NCATS NIH HHS UL1 TR001863NHGRI NIH HHS U54 HG006504NHLBI NIH HHS R01 HL132024NHLBI NIH HHS U01 HL098123NHLBI NIH HHS U01 HL098147NHLBI NIH HHS U01 HL098153NHLBI NIH HHS U01 HL098160NHLBI NIH HHS U01 HL098162NHLBI NIH HHS U01 HL098163NHLBI NIH HHS U01 HL098180NHLBI NIH HHS U01 HL098188NHLBI NIH HHS U01 HL131003NHLBI NIH HHS UM1 HL098123NHLBI NIH HHS UM1 HL098147NHLBI NIH HHS UM1 HL098160NHLBI NIH HHS UM1 HL098162NHLBI NIH HHS UM1 HL128711NICHD NIH HHS T32 HD007149NICHD NIH HHS U54 HD090255NIGMS NIH HHS R01 GM104390NIGMS NIH HHS T32 GM007205NIH HHS S10 OD018521NIH HHS S10 OD018522
Abstract
Congenital heart disease (CHD) is the leading cause of mortality from birth defects. Here, exome sequencing of a single cohort of 2,871 CHD probands, including 2,645 parent-offspring trios, implicated rare inherited mutations in 1.8%, including a recessive founder mutation in GDF1 accounting for ∼5% of severe CHD in Ashkenazim, recessive genotypes in MYH6 accounting for ∼11% of Shone complex, and dominant FLT4 mutations accounting for 2.3% of Tetralogy of Fallot. De novo mutations (DNMs) accounted for 8% of cases, including ∼3% of isolated CHD patients and ∼28% with both neurodevelopmental and extra-cardiac congenital anomalies. Seven genes surpassed thresholds for genome-wide significance, and 12 genes not previously implicated in CHD had >70% probability of being disease related. DNMs in ∼440 genes were inferred to contribute to CHD. Striking overlap between genes with damaging DNMs in probands with CHD and autism was also found.
Indexed as
Genetic Predisposition to DiseaseAdultAutistic DisorderCardiac MyosinsCase-Control StudiesChildExomeFemaleGene ExpressionGenome-Wide Association StudyGrowth Differentiation Factor 1Heart Defects, CongenitalHeterozygoteHigh-Throughput Nucleotide SequencingHomozygoteHumansCardiac MyosinsFLT4 protein, humanGDF1 protein, humanGrowth Differentiation Factor 1MYH6 protein, humanMyosin Heavy ChainsVascular Endothelial Growth Factor Receptor-3
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