Investigating rare pathogenic/likely pathogenic exonic variation in bipolar disorder.


Journal

Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835

Informations de publication

Date de publication:
09 2021
Historique:
received: 02 11 2019
accepted: 16 12 2020
revised: 14 12 2020
pubmed: 24 1 2021
medline: 1 2 2022
entrez: 23 1 2021
Statut: ppublish

Résumé

Bipolar disorder (BD) is a serious mental illness with substantial common variant heritability. However, the role of rare coding variation in BD is not well established. We examined the protein-coding (exonic) sequences of 3,987 unrelated individuals with BD and 5,322 controls of predominantly European ancestry across four cohorts from the Bipolar Sequencing Consortium (BSC). We assessed the burden of rare, protein-altering, single nucleotide variants classified as pathogenic or likely pathogenic (P-LP) both exome-wide and within several groups of genes with phenotypic or biologic plausibility in BD. While we observed an increased burden of rare coding P-LP variants within 165 genes identified as BD GWAS regions in 3,987 BD cases (meta-analysis OR = 1.9, 95% CI = 1.3-2.8, one-sided p = 6.0 × 10

Identifiants

pubmed: 33483695
doi: 10.1038/s41380-020-01006-9
pii: 10.1038/s41380-020-01006-9
pmc: PMC8295400
mid: NIHMS1655878
doi:

Types de publication

Journal Article Meta-Analysis Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5239-5250

Subventions

Organisme : NIMH NIH HHS
ID : R01 MH085543
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH104964
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH077139
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH087979
Pays : United States
Organisme : Medical Research Council
ID : MR/L010305/1
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : R01 MH106527
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH094145
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH085548
Pays : United States
Organisme : NIA NIH HHS
ID : RC2 AG036607
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH095034
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH105653
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH110437
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH123451
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA045508
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH106531
Pays : United States

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© 2021. The Author(s).

Références

Nature. 2014 Feb 13;506(7487):179-84
pubmed: 24463507
Nature. 2016 Aug 17;536(7616):285-91
pubmed: 27535533
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
JAMA Psychiatry. 2016 Jun 1;73(6):590-7
pubmed: 27120077
Nat Genet. 2019 May;51(5):793-803
pubmed: 31043756
Cell. 2011 Jul 22;146(2):247-61
pubmed: 21784246
Arch Gen Psychiatry. 2003 Dec;60(12):1209-15
pubmed: 14662553
Arch Gen Psychiatry. 2009 Jul;66(7):748-55
pubmed: 19581566
PLoS Genet. 2011 Jun;7(6):e1002134
pubmed: 21738484
Acta Psychiatr Scand. 2012 Apr;125(4):293-302
pubmed: 22188017
Arch Gen Psychiatry. 2003 May;60(5):497-502
pubmed: 12742871
Am J Psychiatry. 2004 Oct;161(10):1814-21
pubmed: 15465978
Mol Psychiatry. 2014 Aug;19(8):872-9
pubmed: 24126926
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
Am J Hum Genet. 2017 Jul 6;101(1):5-22
pubmed: 28686856
Genetics. 2015 Aug;200(4):1051-60
pubmed: 26092718
Cell. 2018 Nov 29;175(6):1679-1687.e7
pubmed: 30343897
Nat Genet. 2017 Aug;49(8):1167-1173
pubmed: 28650482
PLoS Comput Biol. 2015 Apr 17;11(4):e1004219
pubmed: 25885710
Nat Genet. 2011 Sep 18;43(10):977-83
pubmed: 21926972
Genomics. 2011 Aug;98(2):79-89
pubmed: 21565264
Genetics. 2015 Aug;200(4):1285-95
pubmed: 26092716
Mol Psychiatry. 2016 Jul;21(7):885-93
pubmed: 27217147
Nat Genet. 2013 Sep;45(9):984-94
pubmed: 23933821
Mol Psychiatry. 2009 Aug;14(8):755-63
pubmed: 19488044
Nat Commun. 2018 Sep 14;9(1):3753
pubmed: 30218074
Nat Protoc. 2015 Oct;10(10):1556-66
pubmed: 26379229
Nature. 2016 Aug 4;536(7614):41-47
pubmed: 27398621
Genome Res. 2010 Sep;20(9):1297-303
pubmed: 20644199
Transl Psychiatry. 2018 Mar 13;8(1):65
pubmed: 29531218
Brain. 2015 Jul;138(Pt 7):2059-73
pubmed: 25935725
Nature. 2020 May;581(7809):434-443
pubmed: 32461654
Transl Psychiatry. 2017 Feb 14;7(2):e1034
pubmed: 28195573
Mol Psychiatry. 2014 Sep;19(9):1017-1024
pubmed: 24280982
Nat Neurosci. 2019 Dec;22(12):1961-1965
pubmed: 31768057
Am J Hum Genet. 2018 Jun 7;102(6):1204-1211
pubmed: 29861106
Genome Res. 2015 Jun;25(6):918-25
pubmed: 25883319
Mol Psychiatry. 2012 Jan;17(1):22-35
pubmed: 21931317
Lancet. 2016 Apr 9;387(10027):1561-1572
pubmed: 26388529
Nature. 2014 Feb 13;506(7487):185-90
pubmed: 24463508
Nature. 2014 Jul 24;511(7510):421-7
pubmed: 25056061
Nat Genet. 2018 Mar;50(3):401-413
pubmed: 29507422
Am J Hum Genet. 2017 Feb 2;100(2):267-280
pubmed: 28132688
Lancet. 2009 Jan 17;373(9659):234-9
pubmed: 19150704
Am J Med Genet C Semin Med Genet. 2003 Nov 15;123C(1):48-58
pubmed: 14601036
Bipolar Disord. 2005 Oct;7(5):449-55
pubmed: 16176438
J Clin Invest. 2009 Apr;119(4):726-36
pubmed: 19339764
Nat Commun. 2014 Mar 11;5:3339
pubmed: 24618891
Nat Genet. 2018 Mar;50(3):381-389
pubmed: 29483656
Arch Gen Psychiatry. 2011 Mar;68(3):241-51
pubmed: 21383262
Genomics. 2011 Dec;98(6):422-30
pubmed: 21903159
Neurosci Biobehav Rev. 2011 Jan;35(3):804-17
pubmed: 20934453
Mol Psychiatry. 2002;7(6):571-8
pubmed: 12140780
Lancet. 2013 May 11;381(9878):1654-62
pubmed: 23663951
Nat Neurosci. 2016 Nov;19(11):1433-1441
pubmed: 27694994
Bipolar Disord. 2016 Aug;18(5):440-50
pubmed: 27566286
Front Biosci (Elite Ed). 2013 Jun 01;5(3):845-63
pubmed: 23747901
JAMA Psychiatry. 2014 Dec 1;71(12):1323-31
pubmed: 25271938
Cell. 2018 Jun 14;173(7):1705-1715.e16
pubmed: 29906448
Biol Psychiatry. 2019 Jul 15;86(2):110-119
pubmed: 30686506
Cell Rep. 2014 Mar 27;6(6):1139-1152
pubmed: 24613350
Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):3576-81
pubmed: 25730879
Mol Psychiatry. 2013 Feb;18(2):195-205
pubmed: 22182935

Auteurs

Xiaoming Jia (X)

Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, 94158, USA.

Fernando S Goes (FS)

Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA.

Adam E Locke (AE)

Division of Genomics & Bioinformatics, Department of Medicine and McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, 63108, USA.

Duncan Palmer (D)

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.

Weiqing Wang (W)

Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.

Sarah Cohen-Woods (S)

Discipline of Psychology and Flinders Centre for Innovation in Cancer, Flinders University, Adelaide, SA, Australia.
Medical Research Council Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Giulio Genovese (G)

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.

Anne U Jackson (AU)

Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.

Chen Jiang (C)

Division of Research, Kaiser Permanente Northern California, Oakland, CA, 94611, USA.

Mark Kvale (M)

Institute for Human Genetics, University of California San Francisco, San Francisco, CA, 94143, USA.

Niamh Mullins (N)

Pamela Sklar Division of Psychiatric Genomics, Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.

Hoang Nguyen (H)

Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.

Mehdi Pirooznia (M)

Bioinformatics and Computational Core, National Heart, Lung, and Blood Institute, Bethesda, MD, 20892, USA.

Margarita Rivera (M)

Medical Research Council Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Department of Biochemistry and Molecular Biology II, Institute of Neurosciences, Center for Biomedical Research, University of Granada, Granada, Spain.

Douglas M Ruderfer (DM)

Departments of Medicine, Psychiatry, and Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.

Ling Shen (L)

Division of Research, Kaiser Permanente Northern California, Oakland, CA, 94611, USA.

Khanh Thai (K)

Division of Research, Kaiser Permanente Northern California, Oakland, CA, 94611, USA.

Matthew Zawistowski (M)

Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.

Yongwen Zhuang (Y)

Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.

Gonçalo Abecasis (G)

Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.

Huda Akil (H)

Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, 48109, USA.

Sarah Bergen (S)

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

Margit Burmeister (M)

Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Human Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Psychiatry, University of Michigan, Ann Arbor, MI, 48109, USA.

Sinéad Chapman (S)

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.

Melissa DelaBastide (M)

Division of Research, Cold Spring Harbor Laboratory, Cold Spring, Harbor, NY, 11797, USA.

Anders Juréus (A)

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

Hyun Min Kang (HM)

Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.

Pui-Yan Kwok (PY)

Institute for Human Genetics, University of California San Francisco, San Francisco, CA, 94143, USA.

Jun Z Li (JZ)

Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Human Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.

Shawn E Levy (SE)

HudsonAlpha Institute for Biotechnology, Huntsville, AL, 35806, USA.

Eric T Monson (ET)

Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA.

Jennifer Moran (J)

Department of Psychiatry, Massachusetts General Hospital, Boston, MA, 02114, USA.

Janet Sobell (J)

Department of Psychiatry and Behavioral Sciences, University of Southern California, Los Angeles, CA, 90033, USA.

Stanley Watson (S)

Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, 48109, USA.

Virginia Willour (V)

Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA.

Sebastian Zöllner (S)

Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Psychiatry, University of Michigan, Ann Arbor, MI, 48109, USA.

Rolf Adolfsson (R)

Departments of Clinical Sciences and Psychiatry, Umea University, Umea, Sweden.

Douglas Blackwood (D)

Division of Psychiatry, University of Edinburgh, Edinburgh, UK.

Michael Boehnke (M)

Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.

Gerome Breen (G)

Medical Research Council Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
NIHR BRC for Mental Health, King's College London, London, UK.

Aiden Corvin (A)

Department of Psychiatry and Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland.

Nick Craddock (N)

Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK.

Arianna DiFlorio (A)

Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK.

Christina M Hultman (CM)

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

Mikael Landen (M)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.

Cathryn Lewis (C)

Medical Research Council Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Department of Medical & Molecular Genetics, King's College London, London, UK.

Steven A McCarroll (SA)

Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA.

W Richard McCombie (W)

Division of Research, Cold Spring Harbor Laboratory, Cold Spring, Harbor, NY, 11797, USA.

Peter McGuffin (P)

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

Andrew McIntosh (A)

Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.

Andrew McQuillin (A)

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

Derek Morris (D)

Department of Psychiatry and Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland.
Discipline of Biochemistry, Neuroimaging and Cognitive Genomics (NICOG) Centre, National University of Ireland Galway, Galway, Ireland.

Richard M Myers (RM)

HudsonAlpha Institute for Biotechnology, Huntsville, AL, 35806, USA.

Michael O'Donovan (M)

Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK.

Roel Ophoff (R)

Center for Neurobehavioral Genetics, University of California Los Angeles, Los Angeles, CA, 90095, USA.
Department of Psychiatry, UMC Utrecht Brain Center Rudolf Magnus, Utrecht, the Netherlands.

Marco Boks (M)

Department of Psychiatry, UMC Utrecht Brain Center Rudolf Magnus, Utrecht, the Netherlands.

Rene Kahn (R)

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.

Willem Ouwehand (W)

Department of Haematology, School of Clinical Medicine, University of Cambridge, Cambridge, UK.

Michael Owen (M)

Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK.

Carlos Pato (C)

Department of Psychiatry and Behavioral Sciences, University of Southern California, Los Angeles, CA, 90033, USA.
SUNY Downstate Medical Center, Brooklyn, NY, 11203, USA.

Michele Pato (M)

Department of Psychiatry and Behavioral Sciences, University of Southern California, Los Angeles, CA, 90033, USA.
Department of Psychiatry, SUNY Downstate Medical Center, Brooklyn, NY, 11203, USA.

Danielle Posthuma (D)

Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Department of Clinical Genetics, Amsterdam Neuroscience, Vrije Universiteit Medical Center, Amsterdam, the Netherlands.

James B Potash (JB)

Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA.

Andreas Reif (A)

Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt am Main, Germany.

Pamela Sklar (P)

Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.

Jordan Smoller (J)

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Department of Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, 02114, USA.

Patrick F Sullivan (PF)

Departments of Genetics and Psychiatry, University of North Carolina, Chapel Hill, NC, USA.

John Vincent (J)

Molecular Neuropsychiatry and Development Laboratory, Campbell Family Mental Health Research Institute, Center for Addiction & Mental Health, Toronto, ON, Canada.
Department of Psychiatry and Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.

James Walters (J)

Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK.

Benjamin Neale (B)

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.

Shaun Purcell (S)

Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.

Neil Risch (N)

Institute for Human Genetics, University of California San Francisco, San Francisco, CA, 94143, USA.

Catherine Schaefer (C)

Division of Research, Kaiser Permanente Northern California, Oakland, CA, 94611, USA.

Eli A Stahl (EA)

Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.

Peter P Zandi (PP)

Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA. pzandi1@jhmi.edu.

Laura J Scott (LJ)

Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, 48109, USA. ljst@umich.edu.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH