Rare coding variants in ten genes confer substantial risk for schizophrenia.

Case-Control Studies Exome Genetic Predisposition to Disease / genetics Humans Mutation Neurodevelopmental Disorders / genetics Receptors, N-Methyl-D-Aspartate / genetics Schizophrenia / genetics

Journal

Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462

Informations de publication

Date de publication:
04 2022
Historique:
received: 13 08 2020
accepted: 16 02 2022
pubmed: 10 4 2022
medline: 23 4 2022
entrez: 9 4 2022
Statut: ppublish

Résumé

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3-50, P < 2.14 × 10

Identifiants

DOI: 10.1038/s41586-022-04556-w PMID: 35396579 PMC: PMC9805802
pubmed: 35396579
doi: 10.1038/s41586-022-04556-w
pii: 10.1038/s41586-022-04556-w
pmc: PMC9805802
mid: NIHMS1854665
doi:

Substances chimiques

Receptors, N-Methyl-D-Aspartate 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

509-516

Subventions

Organisme : NHGRI NIH HHS
ID : U54 HG003067
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH104964
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG064955
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD105351
Pays : United States
Organisme : NIH HHS
ID : 5R01 AG06495502
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH105653
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA024417
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH085548
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH123451
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA037904
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH085521
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH094145
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH124851
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA036216
Pays : United States
Organisme : Medical Research Council
ID : MR/L010305/1
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : U01 MH105666
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH105578
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH116037
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH109539
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG007022
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH105641
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL117626
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer Nature Limited.

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Auteurs

Tarjinder Singh (T)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. tsingh@broadinstitute.org.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. tsingh@broadinstitute.org.
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. tsingh@broadinstitute.org.
ORCID: 0000-0003-0601-6815

Timothy Poterba (T)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

David Curtis (D)

UCL Genetics Institute, University College London, London, UK.
Centre for Psychiatry, Queen Mary University London, London, UK.

Huda Akil (H)

Department of Psychiatry, Michigan Neuroscience Institute, Medical School, University of Michigan, Ann Arbor, MI, USA.

Mariam Al Eissa (M)

Division of Psychiatry, University College London, London, UK.

Jack D Barchas (JD)

Weill Cornell Medical College, New York, NY, USA.

Nicholas Bass (N)

Division of Psychiatry, University College London, London, UK.

Tim B Bigdeli (TB)

Department of Psychiatry and Behavioral Sciences, SUNY Downstate College of Medicine, Brooklyn, NY, USA.

Gerome Breen (G)

Social Genetic and Developmental Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Evelyn J Bromet (EJ)

Department of Psychiatry and Behavioral Health, Health Sciences Center, Stony Brook University, Stony Brook, NY, USA.

Peter F Buckley (PF)

Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.

William E Bunney (WE)

Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA.

Jonas Bybjerg-Grauholm (J)

Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.

William F Byerley (WF)

Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA.

Sinéad B Chapman (SB)

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Wei J Chen (WJ)

College of Public Health, National Taiwan University, Taipei, Taiwan.

Claire Churchhouse (C)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Nicholas Craddock (N)

National Centre for Mental Health, Cardiff University, Cardiff, UK.

Caroline M Cusick (CM)

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Lynn DeLisi (L)

Department of Psychiatry, Cambridge Health Alliance, Cambridge Hospital, Cambridge, MA, USA.

Sheila Dodge (S)

Genomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Michael A Escamilla (MA)

Texas Tech University Health Sciences Center, El Paso, TX, USA.

Saana Eskelinen (S)

University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Department of Public Health Solutions, Mental Health Unit, National Institute for Health and Welfare, Helsinki, Finland.

Ayman H Fanous (AH)

Department of Psychiatry and Behavioral Sciences, SUNY Downstate Medical Center, Brooklyn, NY, USA.

Stephen V Faraone (SV)

Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA.

Alessia Fiorentino (A)

Division of Psychiatry, University College London, London, UK.

Laurent Francioli (L)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Stacey B Gabriel (SB)

Genomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Diane Gage (D)

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Sarah A Gagliano Taliun (SA)

Faculté de Médecine, Université de Montréal, Montreal, Quebec, Canada.
Montréal Heart Institute, Montreal, Quebec, Canada.

Andrea Ganna (A)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.

Giulio Genovese (G)

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

David C Glahn (DC)

Department of Psychiatry, Boston Children's Hospital, Boston, MA, USA.

Jakob Grove (J)

Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
Department of Biomedicine and Center for Integrative Sequencing, Aarhus University, Aarhus, Denmark.
Center for Genomics and Personalized Medicine, Aarhus, Denmark.
Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark.

Mei-Hua Hall (MH)

McLean Hospital, Harvard Medical School, Belmont, MA, USA.

Eija Hämäläinen (E)

Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.

Henrike O Heyne (HO)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.

Matti Holi (M)

Department of Psychiatry, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.

David M Hougaard (DM)

Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.

Daniel P Howrigan (DP)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Hailiang Huang (H)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Hai-Gwo Hwu (HG)

Department of Psychiatry, National Taiwan University, Taipei, Taiwan.

René S Kahn (RS)

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
MIRECC, JP Peters VA Hospital, Bronx, NY, USA.

Hyun Min Kang (HM)

Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.

Konrad J Karczewski (KJ)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

George Kirov (G)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.

James A Knowles (JA)

Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY, USA.

Francis S Lee (FS)

Weill Cornell Medical College, New York, NY, USA.

Douglas S Lehrer (DS)

Department of Psychiatry, Wright State University, Dayton, OH, USA.

Francesco Lescai (F)

Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
Department of Biomedicine, Aarhus University, Aarhus, Denmark.

Dolores Malaspina (D)

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Stephen R Marder (SR)

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Steven A McCarroll (SA)

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Genetics, Harvard Medical School, Boston, MA, USA.

Andrew M McIntosh (AM)

University of Edinburgh, Edinburgh, UK.

Helena Medeiros (H)

Department of Psychiatry and Behavioral Sciences, SUNY Downstate Medical Center, Brooklyn, NY, USA.

Lili Milani (L)

Institute of Genomics, University of Tartu, Tartu, Estonia.

Christopher P Morley (CP)

Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA.
Department of Public Health and Preventive Medicine and Department of Family Medicine, SUNY Upstate Medical University, Syracuse, NY, USA.

Derek W Morris (DW)

National University of Ireland, Galway, Ireland.

Preben Bo Mortensen (PB)

Aarhus University, Aarhus, Denmark.

Richard M Myers (RM)

HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.

Merete Nordentoft (M)

Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
Copenhagen Research Center for Mental Health, Mental Health Services, Copenhagen University Hospital, Copenhagen, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

Niamh L O'Brien (NL)

Division of Psychiatry, University College London, London, UK.

Ana Maria Olivares (AM)

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Dost Ongur (D)

McLean Hospital, Harvard Medical School, Belmont, MA, USA.

Willem H Ouwehand (WH)

University of Cambridge, Cambridge, UK.

Duncan S Palmer (DS)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Tiina Paunio (T)

Department of Psychiatry, University of Helsinki, Helsinki, Finland.

Digby Quested (D)

Oxford Health NHS Foundation Trust, Oxford, UK.

Mark H Rapaport (MH)

Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA.

Elliott Rees (E)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.

Brandi Rollins (B)

Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA.

F Kyle Satterstrom (FK)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.

Alan Schatzberg (A)

Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.

Edward Scolnick (E)

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Laura J Scott (LJ)

Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.

Sally I Sharp (SI)

Division of Psychiatry, University College London, London, UK.

Pamela Sklar (P)

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Jordan W Smoller (JW)

Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
Department of Psychiatry, Harvard Medical School, Boston, MA, USA.

Janet L Sobell (JL)

Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Matthew Solomonson (M)

Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Eli A Stahl (EA)

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Christine R Stevens (CR)

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Jaana Suvisaari (J)

Finnish Institute for Health and Welfare, Helsinki, Finland.

Grace Tiao (G)

Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Stanley J Watson (SJ)

Department of Psychiatry, Michigan Neuroscience Institute, Medical School, University of Michigan, Ann Arbor, MI, USA.

Nicholas A Watts (NA)

Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Douglas H Blackwood (DH)

Department of Psychiatry, University of Edinburgh, Edinburgh, UK.

Anders D Børglum (AD)

Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
Department of Biomedicine and Center for Integrative Sequencing, Aarhus University, Aarhus, Denmark.
Center for Genomics and Personalized Medicine, Aarhus, Denmark.

Bruce M Cohen (BM)

McLean Hospital, Harvard Medical School, Belmont, MA, USA.

Aiden P Corvin (AP)

Trinity College Dublin, Dublin, Ireland.

Tõnu Esko (T)

Institute of Genomics, University of Tartu, Tartu, Estonia.

Nelson B Freimer (NB)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Stephen J Glatt (SJ)

Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA.

Christina M Hultman (CM)

School of Medicine, Johns Hopkins University, Baltimore, MD, USA.

Andrew McQuillin (A)

Division of Psychiatry, University College London, London, UK.

Aarno Palotie (A)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.

Carlos N Pato (CN)

Department of Psychiatry and Behavioral Sciences, SUNY Downstate College of Medicine, Brooklyn, NY, USA.

Michele T Pato (MT)

Department of Psychiatry and Behavioral Sciences, SUNY Downstate College of Medicine, Brooklyn, NY, USA.

Ann E Pulver (AE)

School of Medicine, Johns Hopkins University, Baltimore, MD, USA.

David St Clair (D)

University of Aberdeen, Aberdeen, UK.

Ming T Tsuang (MT)

Center for Behavioral Genomics, Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.

Marquis P Vawter (MP)

Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA.

James T Walters (JT)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.

Thomas M Werge (TM)

Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, Copenhagen, Denmark.
Center for GeoGenetics, GLOBE Institute, University of Copenhagen, Copenhagen, Denmark.

Roel A Ophoff (RA)

Center for Neurobehavioral Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Psychiatry, Erasmus Medical Center, Erasmus University, Rotterdam, the Netherlands.

Patrick F Sullivan (PF)

Karolinska Institute, Solna, Sweden.
University of North Carolina, Chapel Hill, NC, USA.

Michael J Owen (MJ)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.

Michael Boehnke (M)

Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.

Michael C O'Donovan (MC)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.

Benjamin M Neale (BM)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. bneale@broadinstitute.org.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. bneale@broadinstitute.org.
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. bneale@broadinstitute.org.
ORCID: 0000-0003-1513-6077

Mark J Daly (MJ)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. mjdaly@atgu.mgh.harvard.edu.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. mjdaly@atgu.mgh.harvard.edu.
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. mjdaly@atgu.mgh.harvard.edu.
Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland. mjdaly@atgu.mgh.harvard.edu.
ORCID: 0000-0002-0949-8752

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Classifications MeSH

questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études cas-témoins › Rare coding variants in ten genes confer...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Exome › Rare coding variants in ten genes confer...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Rare coding variants in ten genes confer...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Rare coding variants in ten genes confer...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Rare coding variants in ten genes confer...
questionsmedicales.fr › Troubles mentaux › Troubles du développement neurologique › Rare coding variants in ten genes confer...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs aux neuromédiateurs › Récepteurs aux acides aminés › Récepteurs au glutamate › Récepteurs ionotropes du glutamate › Récepteurs du N-méthyl-D-aspartate › Rare coding variants in ten genes confer...
questionsmedicales.fr › Troubles mentaux › Schizophrénie et troubles avec traits psychotiques › Schizophrénie › Rare coding variants in ten genes confer...