Genomic analyses implicate noncoding de novo variants in congenital heart disease.


Journal

Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904

Informations de publication

Date de publication:
08 2020
Historique:
received: 09 03 2019
accepted: 22 05 2020
pubmed: 1 7 2020
medline: 27 10 2020
entrez: 1 7 2020
Statut: ppublish

Résumé

A genetic etiology is identified for one-third of patients with congenital heart disease (CHD), with 8% of cases attributable to coding de novo variants (DNVs). To assess the contribution of noncoding DNVs to CHD, we compared genome sequences from 749 CHD probands and their parents with those from 1,611 unaffected trios. Neural network prediction of noncoding DNV transcriptional impact identified a burden of DNVs in individuals with CHD (n = 2,238 DNVs) compared to controls (n = 4,177; P = 8.7 × 10

Identifiants

pubmed: 32601476
doi: 10.1038/s41588-020-0652-z
pii: 10.1038/s41588-020-0652-z
pmc: PMC7415662
mid: NIHMS1597372
doi:

Substances chimiques

RNA, Untranslated 0
RNA-Binding Proteins 0

Types de publication

Clinical Trial Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

769-777

Subventions

Organisme : NHLBI NIH HHS
ID : UM1 HL098162
Pays : United States
Organisme : NICHD NIH HHS
ID : T32 HD075735
Pays : United States
Organisme : NCATS NIH HHS
ID : U2C TR002818
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM120609
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL131003
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL057181
Pays : United States
Organisme : NHLBI NIH HHS
ID : UM1 HL098166
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM071966
Pays : United States
Organisme : NHLBI NIH HHS
ID : UM1 HL128761
Pays : United States
Organisme : NHLBI NIH HHS
ID : UM1 HL098147
Pays : United States
Organisme : NHLBI NIH HHS
ID : R24 HL123879
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL098147
Pays : United States
Organisme : NHLBI NIH HHS
ID : R03 HL147197
Pays : United States
Organisme : NHLBI NIH HHS
ID : UM1 HL098123
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002538
Pays : United States
Organisme : NHLBI NIH HHS
ID : R03 HL138352
Pays : United States
Organisme : NIH HHS
ID : S10 OD018522
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL098153
Pays : United States
Organisme : NIH HHS
ID : S10 OD026880
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL098163
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007280
Pays : United States
Organisme : NICHD NIH HHS
ID : U24 HD090743
Pays : United States
Organisme : NHLBI NIH HHS
ID : UM1 HL128711
Pays : United States

Commentaires et corrections

Type : CommentIn

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Auteurs

Felix Richter (F)

Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Sarah U Morton (SU)

Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Division of Newborn Medicine, Boston Children's Hospital, Boston, MA, USA.

Seong Won Kim (SW)

Department of Genetics, Harvard Medical School, Boston, MA, USA.

Alexander Kitaygorodsky (A)

Departments of Systems Biology and Biomedical Informatics, Columbia University, New York, NY, USA.

Lauren K Wasson (LK)

Department of Genetics, Harvard Medical School, Boston, MA, USA.

Kathleen M Chen (KM)

Flatiron Institute, Simons Foundation, New York, NY, USA.

Jian Zhou (J)

Flatiron Institute, Simons Foundation, New York, NY, USA.
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Hongjian Qi (H)

Departments of Systems Biology and Biomedical Informatics, Columbia University, New York, NY, USA.

Nihir Patel (N)

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Steven R DePalma (SR)

Department of Genetics, Harvard Medical School, Boston, MA, USA.

Michael Parfenov (M)

Department of Genetics, Harvard Medical School, Boston, MA, USA.

Jason Homsy (J)

Department of Genetics, Harvard Medical School, Boston, MA, USA.
Center for External Innovation, Takeda Pharmaceuticals USA, Cambridge, MA, USA.

Joshua M Gorham (JM)

Department of Genetics, Harvard Medical School, Boston, MA, USA.

Kathryn B Manheimer (KB)

Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Sema4, Stamford, CT, USA.

Matthew Velinder (M)

Department of Human Genetics, Utah Center for Genetic Discovery, University of Utah School of Medicine, Salt Lake City, UT, USA.

Andrew Farrell (A)

Department of Human Genetics, Utah Center for Genetic Discovery, University of Utah School of Medicine, Salt Lake City, UT, USA.

Gabor Marth (G)

Department of Human Genetics, Utah Center for Genetic Discovery, University of Utah School of Medicine, Salt Lake City, UT, USA.

Eric E Schadt (EE)

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Sema4, Stamford, CT, USA.
Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Jonathan R Kaltman (JR)

Heart Development and Structural Diseases Branch, Division of Cardiovascular Sciences, NHLBI/NIH, Bethesda, MD, USA.

Jane W Newburger (JW)

Boston Children's Hospital, Boston, MA, USA.

Alessandro Giardini (A)

Cardiorespiratory Unit, Great Ormond Street Hospital, London, UK.

Elizabeth Goldmuntz (E)

Division of Cardiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Martina Brueckner (M)

Departments of Pediatrics and Genetics, Yale University School of Medicine, New Haven, CT, USA.

Richard Kim (R)

Children's Hospital Los Angeles, Los Angeles, CA, USA.

George A Porter (GA)

Department of Pediatrics, University of Rochester, Rochester, NY, USA.

Daniel Bernstein (D)

Department of Pediatrics, Stanford University, Palo Alto, CA, USA.

Wendy K Chung (WK)

Departments of Pediatrics and Medicine, Columbia University Medical Center, New York, NY, USA.

Deepak Srivastava (D)

Gladstone Institute of Cardiovascular Disease and University of California San Francisco, San Francisco, CA, USA.

Martin Tristani-Firouzi (M)

Division of Pediatric Cardiology, University of Utah School of Medicine, Salt Lake City, UT, USA.

Olga G Troyanskaya (OG)

Flatiron Institute, Simons Foundation, New York, NY, USA.
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
Department of Computer Science, Princeton University, Princeton, NJ, USA.

Diane E Dickel (DE)

Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Lab, Berkeley, CA, USA.

Yufeng Shen (Y)

Departments of Systems Biology and Biomedical Informatics, Columbia University, New York, NY, USA.

Jonathan G Seidman (JG)

Department of Genetics, Harvard Medical School, Boston, MA, USA.

Christine E Seidman (CE)

Department of Genetics, Harvard Medical School, Boston, MA, USA.
Department of Cardiology, Brigham and Women's Hospital, Boston, MA, USA.

Bruce D Gelb (BD)

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. bruce.gelb@mssm.edu.
Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. bruce.gelb@mssm.edu.
Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA. bruce.gelb@mssm.edu.

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