Mapping genomic loci implicates genes and synaptic biology in schizophrenia
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem
Grantová podpora
MC_UU_00007/10
Medical Research Council - United Kingdom
R01 MH116281
NIMH NIH HHS - United States
5R01 MH101519
NIH HHS - United States
085475/B/08/Z
Wellcome Trust - United Kingdom
G1100583
Medical Research Council - United Kingdom
R01 MH124873
NIMH NIH HHS - United States
U01 MH109536
NIMH NIH HHS - United States
R01 MH101519
NIMH NIH HHS - United States
Wellcome Trust - United Kingdom
MR/L010305/1
Medical Research Council - United Kingdom
G0901310
Medical Research Council - United Kingdom
085475/Z/08/Z
Wellcome Trust - United Kingdom
R01 MH119243
NIMH NIH HHS - United States
G0800509
Medical Research Council - United Kingdom
R01 MH106575
NIMH NIH HHS - United States
R37 NS036715
NINDS NIH HHS - United States
K01 MH121659
NIMH NIH HHS - United States
U01 MH109514
NIMH NIH HHS - United States
PubMed
35396580
PubMed Central
PMC9392466
DOI
10.1038/s41586-022-04434-5
PII: 10.1038/s41586-022-04434-5
Knihovny.cz E-zdroje
- MeSH
- alely MeSH
- celogenomová asociační studie * MeSH
- genetická predispozice k nemoci genetika MeSH
- genomika MeSH
- jednonukleotidový polymorfismus genetika MeSH
- lidé MeSH
- schizofrenie * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies.
2nd Opinion Outpatient Clinic GGNet Mental Health Warnsveld The Netherlands
Altrecht General Menthal Health Care Utrecht The Netherlands
Analytic and Translational Genetics Unit Massachusetts General Hospital Boston MA USA
APC Microbiome Ireland University College Cork Cork Ireland
Área de Psiquiatría Universidad de Oviedo Hospital Universitario Central de Asturias Asturias Spain
Arkin Institute for Mental Health Amsterdam The Netherlands
Asfalia Biologics iPEPS ICM Hôpital Universitaire de la Pitié Salpêtrière Paris France
Baker Heart and Diabetes Institute Melbourne Victoria Australia
Banner University Medical Center Phoenix AZ USA
Barnet Enfield and Haringey Mental Health NHS Trust St Ann's Hospital London UK
Berlin Institute of Health Berlin Germany
Berlin School of Mind and Brain Humboldt Universität zu Berlin Berlin Germany
Biomedical Research Institute INCLIVA Valencia Spain
Black Dog Institute University of New South Wales Randwick New South Wales Australia
Brain and Mind Centre The University of Sydney Sydney New South Wales Australia
Broad Institute of MIT and Harvard Cambridge MA USA
Bulgarian Academy of Science Sofia Bulgaria
Cambridge Health Alliance Cambridge MA USA
Castle Peak Hospital Hong Kong China
Center for Bioinformatics Department of Informatics University of Oslo Oslo Norway
Center for Depression Anxiety and Stress Research McLean Hospital Belmont MA USA
Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences Kunming China
Center for Genomics and Personalized Medicine Aarhus Denmark
Center for GeoGenetics GLOBE Institute University of Copenhagen Copenhagen Denmark
Center for Neuropsychiatric Research National Health Research Institutes Zhunan Town Taiwan
Center for Psychiatric Genetics NorthShore University HealthSystem Evanston IL USA
Center for Psychopharmacology Diakonhjemmet Hospital Oslo Norway
Centre for Human Genetics University of Marburg Marburg Germany
Centre for Neuroimaging Cognition and Genomics National University of Ireland Galway Galway Ireland
Centre for PanorOmic Sciences LKS Faculty of Medicine The University of Hong Kong Hong Kong China
Centre for Psychiatry Queen Mary University London London UK
Centre for Public Health Institute of Clinical Sciences Queen's University Belfast Belfast UK
Centre Hospitalier du Rouvray Rouen France
Centro de Investigación Biomédica en Red de Salud Mental Oviedo Asturias Spain
Centro de Investigación Biomédica en Red en Salud Mental Madrid Spain
Children's Hospital of Philadelphia Leonard Madlyn Abramson Research Center Philadelphia PA USA
Clinic of Psychiatry and Psychotherapy Weißer Hirsch Dresden Germany
Clinical Neuroscience Max Planck Institute of Experimental Medicine Göttingen Germany
College of Medicine SUNY Downstate Health Sciences University New York NY USA
College of Public Health China Medical University Taichung Taiwan
Comedicum Lindwurmhof Munich Germany
Computational Research Division Lawrence Berkeley National Laboratory Berkeley CA USA
Dementia Research Institute Cardiff University Cardiff UK
Department for Neurosciences Center for Contextual Psychiatry KU Leuven Leuven Belgium
Department of Biomedical and Neuromotor Sciences University of Bologna Bologna Italy
Department of Biomedical Data Science Stanford University Stanford CA USA
Department of Biomedicine Aarhus University Aarhus Denmark
Department of Biomedicine and Centre for Integrative Sequencing Aarhus University Aarhus Denmark
Department of Biomedicine University of Basel Basel Switzerland
Department of Cellular Computational and Integrative Biology University of Trento Trento Italy
Department of Clinical Medicine University of Copenhagen Copenhagen Denmark
Department of Clinical Sciences Psychiatry Umeå University Umeå Sweden
Department of Community Health and Epidemiology Dalhousie University Halifax Nova Scotia Canada
Department of Computer Science University of North Carolina Chapel Hill NC USA
Department of Genetics and Genomics Icahn School of Medicine at Mount Sinai New York NY USA
Department of Genetics Faculty of Biological Sciences Universidad de Valencia Valencia Spain
Department of Genetics Faculty of Biology Sofia University St Kliment Ohridski Sofia Bulgaria
Department of Genetics University of North Carolina Chapel Hill NC USA
Department of Health Data Science University of Liverpool Liverpool UK
Department of Health Sciences University of Leicester Leicester UK
Department of Mathematics and Statistics University of Helsinki Helsinki Finland
Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
Department of Medical Genetics Medical School University of Pécs Pécs Hungary
Department of Medical Genetics Medical University Sofia Bulgaria
Department of Medical Genetics Oslo University Hospital Oslo Norway
Department of Medical Genetics University Medical Centre Utrecht Utrecht The Netherlands
Department of Medical Genetics University of Pécs School of Medicine Pécs Hungary
Department of Medicine Harvard Medical School Boston MA USA
Department of Mental Health ASL Rome 1 Rome Italy
Department of Mental Health Norwegian University of Science and Technology Trondheim Norway
Department of Molecular and Translational Medicine University of Brescia Brescia Italy
Department of Neurology Medical University of Vienna Vienna Austria
Department of Neuroscience Dokuz Eylül University Graduate School of Health Sciences Izmir Turkey
Department of Neuroscience Icahn School of Medicine at Mount Sinai New York NY USA
Department of Neurosciences Center for Clinical Psychiatry KU Leuven Leuven Belgium
Department of Pharmacy University of Oslo Oslo Norway
Department of Psychiatric Research Diakonhjemmet Hospital Oslo Norway
Department of Psychiatry Academic Medical Centre University of Amsterdam Amsterdam The Netherlands
Department of Psychiatry and Behavioral Neurosciences The University of Chicago Chicago IL USA
Department of Psychiatry and Behavioral Sciences Emory University Atlanta GA USA
Department of Psychiatry and Behavioral Sciences Stanford University Stanford CA USA
Department of Psychiatry and Behavioral Sciences SUNY Upstate Medical University Syracuse NY USA
Department of Psychiatry and Behavioral Sciences The Johns Hopkins University Baltimore MD USA
Department of Psychiatry and Behavioral Sciences University of Washington Seattle WA USA
Department of Psychiatry and Behavioural Health Stony Brook University Stony Brook NY USA
Department of Psychiatry and Neurobehavioural Sciences University College Cork Cork Ireland
Department of Psychiatry and Psychotherapy Charité Universitätsmedizin Berlin Germany
Department of Psychiatry and Psychotherapy Jena University Hospital Jena Germany
Department of Psychiatry and Psychotherapy Medical University of Vienna Vienna Austria
Department of Psychiatry and Psychotherapy University Medical Center Göttingen Göttingen Germany
Department of Psychiatry and the Behavioral Sciences SUNY Downstate Medical Center New York NY USA
Department of Psychiatry Charité Universitätsmedizin Berlin Berlin Germany
Department of Psychiatry Charité Universitätsmedizin Berlin Germany
Department of Psychiatry Chonnam National University Medical School Gwangju Korea
Department of Psychiatry Columbia University New York NY USA
Department of Psychiatry Dalhousie University Halifax Nova Scotia Canada
Department of Psychiatry Dokuz Eylül University School of Medicine Izmir Turkey
Department of Psychiatry Erasmus University Medical Center Rotterdam The Netherlands
Department of Psychiatry Faculty of Medicine Istanbul University Istanbul Turkey
Department of Psychiatry Fujita Health University School of Medicine Toyoake Aichi Japan
Department of Psychiatry GGz Centraal Utrecht The Netherlands
Department of Psychiatry Hadassah Hebrew University Medical Center Jerusalem Israel
Department of Psychiatry Harvard Medical School Boston MA USA
Department of Psychiatry Icahn School of Medicine at Mount Sinai New York NY USA
Department of Psychiatry Irmandade da Santa Casa de Misericórdia de São Paulo São Paulo Brazil
Department of Psychiatry Landspitali University Hospital Reykjavik Iceland
Department of Psychiatry LKS Faculty of Medicine The University of Hong Kong Hong Kong China
Department of Psychiatry Massachusetts General Hospital Boston MA USA
Department of Psychiatry McGill University Montreal Québec Canada
Department of Psychiatry Monash University Melbourne Victoria Australia
Department of Psychiatry National Taiwan University Hospital Taipei Taiwan
Department of Psychiatry Phoenix VA Healthcare System Phoenix AZ USA
Department of Psychiatry Queens University Kingston Kingston Ontario Canada
Department of Psychiatry Research Unit of Clinical Neuroscience University of Oulu Oulu Finland
Department of Psychiatry Royal College of Surgeons in Ireland Dublin Ireland
Department of Psychiatry San Cecilio University Hospital University of Granada Granada Spain
Department of Psychiatry School of Medicine Ankara University Ankara Turkey
Department of Psychiatry The 1st Affiliated Hospital of Xi'an Jiaotong University Xi'an China
Department of Psychiatry The Chinese University of Hong Kong Hong Kong China
Department of Psychiatry Universidade Federal de São Paulo São Paulo Brazil
Department of Psychiatry University of California San Diego La Jolla CA USA
Department of Psychiatry University of California San Francisco San Francisco CA USA
Department of Psychiatry University of Colorado Denver Aurora CO USA
Department of Psychiatry University of Helsinki Helsinki Finland
Department of Psychiatry University of Iowa Carver College of Medicine Iowa City IA USA
Department of Psychiatry University of Melbourne Parkville Victoria Australia
Department of Psychiatry University of Münster Münster Germany
Department of Psychiatry University of North Carolina Chapel Hill NC USA
Department of Psychiatry University of Oxford Oxford UK
Department of Psychiatry University of Pennsylvania Philadelphia PA USA
Department of Psychiatry University of Pittsburgh Pittsburgh PA USA
Department of Psychiatry University of Toronto Toronto Ontario Canada
Department of Psychiatry Veterans Affairs New York Harbor Healthcare System New York NY USA
Department of Psychiatry Washington University St Louis MO USA
Department of Psychiatry Wright State University Dayton OH USA
Department of Psychiatry Yale School of Medicine New Haven CT USA
Department of Psychiatry Zucker School of Medicine at Hofstra Northwell Hempstead NY USA
Department of Psychology Harvard University Cambridge MA USA
Department of Psychology University of Chinese Academy of Sciences Beijing China
Department of Psychosis Institute of Mental Health Singapore Singapore
Department of Public Health University of Helsinki Helsinki Finland
Department of Stem Cell and Regenerative Biology Harvard University Cambridge MA USA
Departments of Psychiatry and Human Genetics University of Chicago Chicago IL USA
Dipartimento di Biologia Universita' di Pisa Pisa Italy
Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda MD USA
Division of Medical Genetics Department of Biomedicine University of Basel Basel Switzerland
Division of Mental Health and Addiction Oslo University Hospital Oslo Norway
Division of Mental Health St Olav's Hospital Trondheim University Hospital Trondheim Norway
Division of Molecular Medicine NSW Health Pathology North Newcastle New South Wales Australia
Division of Psychiatry Department of Mental Health Neuroscience University College London London UK
Division of Psychiatry Research Zucker Hillside Hospital Glen Oaks NY USA
Early Clinical Development Pfizer Worldwide Research and Development Groton CT USA
eCODE Genetics Amgen Reykjavik Iceland
Eli Lilly and Company Windlesham UK
Estonian Genome Center Institute of Genomics University of Tartu Tartu Estonia
Faculty of Medicine University of Iceland Reykjavik Iceland
Faculty of Medicine Vilnius University Vilnius Lithuania
Faculty of Science Medicine and Health University of Wollongong Wollongong New South Wales Australia
Folkhälsan Research Center Helsinki Finland
Genetic Unit IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli Brescia Italy
Health Science Center University of Tennessee Memphis TN USA
Hospital Universitari Institut Pere Mata IISPV Universitat Rovira i Virgili CIBERSAM Reus Spain
Human Genetics Genome Institute of Singapore A*STAR Singapore Singapore
Hunter Medical Research Institute Newcastle New South Wales Australia
Hunter New England Health and University of Newcastle Newcastle New South Wales Australia
Illawarra Health and Medical Research Institute Wollongong New South Wales Australia
INSERM U1266 Institut de Psychiatrie et de Neurosciences Paris France
Institute for Behavioural Genetics University of Colorado Boulder Boulder CO USA
Institute for Genomic Health SUNY Downstate Medical Center New York NY USA
Institute for Molecular Bioscience University of Queensland Brisbane Queensland Australia
Institute for Molecular Medicine Finland University of Helsinki Helsinki Finland
Institute of Behavioral Science Feinstein Institutes for Medical Research Manhasset NY USA
Institute of Genomic Medicine University of California San Diego La Jolla CA USA
Institute of Human Genetics University of Bonn Bonn Germany
Institute of Medical Genetics and Pathology University Hospital Basel Basel Switzerland
Institute of Medical Psychology Faculty of Medicine University of Coimbra Coimbra Portugal
Institute of Medical Sciences University of Aberdeen Aberdeen UK
Institute of Molecular Genetics of National Research Centre Kurchatov Institute Moscow Russia
Institute of Neuroscience and Medicine Research Center Juelich Juelich Germany
Institute of Neurosciences Biomedical Research Center University of Granada Granada Spain
Institute of Psychiatric Phenomics and Genomics University Hospital LMU Munich Munich Germany
Institute of Psychology Chinese Academy of Science Beijing China
Instituto de Investigación Sanitaria del Principado de Asturias Oviedo Asturias Spain
Instituto de Investigación Sanitaria Santiago de Compostela Spain
James J Peters VA Medical Center Bronx NY USA
Laboratory for Statistical Analysis RIKEN Center for Integrative Medical Sciences Yokohama Japan
Laboratory of Integrative Neuroscience Universidade Federal de São Paulo São Paulo Brazil
Latvian Biomedical Research and Study Centre Riga Latvia
Lee Kong Chian School of Medicine Nanyang Technological University Singapore Singapore
Lieber Institute for Brain Development Baltimore MD USA
Massachusetts Mental Health Center Boston MA USA
Mater Research Institute University of Queensland Brisbane Queensland Australia
Max Planck Institute of Psychiatry Munich Germany
Medical Research Center Oulu Oulu University Hospital and University of Oulu Oulu Finland
Mental Health Research Center Moscow Russian Federation
Mental Illness Research Clinical and Education Center JJ Peters VA Medical Center New York NY USA
Menzies Institute for Medical Research University of Tasmania Hobart Tasmania Australia
Molecular and Cellular Therapeutics Royal College of Surgeons in Ireland Dublin Ireland
Molecular Psychiatry Laboratory Division of Psychiatry University College London London UK
Munich Cluster for Systems Neurology Munich Germany
National Centre for Register based Research Aarhus University Aarhus Denmark
Neurobiology and Cognitive Science Center National Taiwan University Taipei Taiwan
Neuroscience Research Australia Sydney New South Wales Australia
Neuroscience Therapeutic Area Janssen Research and Development Titusville NJ USA
NORMENT Centre Department of Clinical Science University of Bergen Bergen Norway
NORMENT Centre Division of Mental Health and Addiction University of Oslo Oslo Norway
NORMENT Centre Institute of Clinical Medicine University of Oslo Oslo Norway
Northern Adelaide Local Health Network Adelaide South Australia Australia
NorthWestern Mental Health Melbourne Victoria Australia
Oxford Health NHS Foundation Trust Oxford UK
Oxford Health NHS Foundation Trust Warneford Hospital Oxford UK
Peking University Sixth Hospital Peking University Institute of Mental Health Beijing China
PKU IDG McGovern Institute for Brain Research Peking University Beijing China
Program in Medical and Population Genetics The Broad Institute of MIT and Harvard Cambridge MA USA
Psychiatric Clinic Alexandrovska University Hospital Sofia Bulgaria
Psychiatry Unit IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli Brescia Italy
Psychosis Research Unit Aarhus University Hospital Aarhus Denmark
Queensland Brain Institute University of Queensland Brisbane Queensland Australia
Queensland Centre for Mental Health Research University of Queensland Brisbane Queensland Australia
Ramsay Health Care Mental Health Adelaide South Australia Australia
Regeneron Genetics Center Orange CA USA
Research Division Institute of Mental Health Singapore Republic of Singapore
Rheumatology Research Group Vall d'Hebron Research Institute Barcelona Spain
RIKEN Center for Integrative Medical Sciences Yokohama Japan
Rutgers University New Jersey Medical School Newark NJ USA
Rutgers University Robert Wood Johnson Medical School New Brunswick NJ USA
School of Biomedical Sciences The Chinese University of Hong Kong Hong Kong China
School of Life Science and Technology ShanghaiTech University Shanghai China
School of Life Sciences Westlake University Hangzhou China
School of Medicine and Public Health University of Newcastle Newcastle New South Wales Australia
School of Medicine University of Queensland Herston Queensland Australia
School of Nursing Louisiana State University Health Sciences Center New Orleans LA USA
School of Psychiatry University of New South Wales Sydney New South Wales Australia
School of Psychology University of Newcastle Newcastle New South Wales Australia
School of Social and Health Sciences Leeds Trinity University Leeds UK
Semel Institute for Neurosciene University of California Los Angeles Los Angeles CA USA
Sheba Medical Center Tel Hashomer Israel
Sheppard Pratt Health System Baltimore MD USA
South Australian Health and Medical Research Institute Adelaide South Australia Australia
South London and Maudsley NHS Mental Health Foundation Trust London UK
St Vincent's Hospital Melbourne Victoria Australia
Stanley Center for Psychiatric Research Broad Institute of MIT and Harvard Cambridge MA USA
Stanley Neurovirology Laboratory Johns Hopkins University School of Medicine Baltimore MD USA
SUNY Upstate Medical University Syracuse NY USA
The Lundbeck Foundation Initiative for Integrative Psychiatric Research Aarhus Denmark
The Lundbeck Foundation Initiative for Integrative Psychiatric Research iPSYCH Copenhagen Denmark
THL Finnish Institute for Health and Welfare Helsinki Finland
TIPS Network for Clinical Research in Psychosis Stavanger University Hospital Stavanger Norway
UCL Genetics Institute University College London London UK
UFR Santé Université de Rouen Normandie Rouen France
Université de Paris Faculté de Médecine Hôpital Cochin Tarnier Paris France
University Medical Center Utrecht Department of Psychiatry Utrecht The Netherlands
University of Nicosia Medical School Nicosia Cyprus
University of Sevilla CIBERSAM IBiS Seville Spain
VA Boston Health Care System Brockton MA USA
VA Greater Los Angeles Healthcare System Los Angeles CA USA
VA Puget Sound Health Care System Seattle WA USA
West Region Institute of Mental Health Singapore Singapore
Westlake Laboratory of Life Sciences and Biomedicine Hangzhou China
Yoo Loo Lin School of Medicine National University of Singapore Singapore Singapore
Zobrazit více v PubMed
Owen MJ Sawa A.& Mortensen PB Schizophrenia. The Lancet vol. 388 86–97 (2016). PubMed PMC
Plana-Ripoll O.et al. A comprehensive analysis of mortality-related health metrics associated with mental disorders: a nationwide, register-based cohort study. Lancet 394, 1827–1835 (2019). PubMed
Momen NC et al. Association between mental disorders and subsequent medical conditions. N. Engl. J. Med 382, 1721–1731 (2020). PubMed PMC
Jääskeläinen E.et al. A systematic review and meta-analysis of recovery in schizophrenia. Schizophr Bull. 39, 1296–1306 (2013). PubMed PMC
Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460, 748–752 (2009). PubMed PMC
Pocklington AJ et al. Novel Findings from CNVs Implicate Inhibitory and Excitatory Signaling Complexes in Schizophrenia. Neuron 86, 1203–1214 (2015). PubMed PMC
Singh T.et al. The contribution of rare variants to risk of schizophrenia in individuals with and without intellectual disability. Nat. Genet 49, 1167–1173 (2017). PubMed PMC
Rees E.et al. De novo mutations identified by exome sequencing implicate rare missense variants in SLC6A1 in schizophrenia. Nat. Neurosci (2020) doi:10.1038/s41593-019-0565-2. PubMed DOI PMC
Lam M.et al. Comparative genetic architectures of schizophrenia in East Asian and European populations. Nat. Genet (2019) doi:10.1038/s41588-019-0512-x. PubMed DOI PMC
Bigdeli TB et al. Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry. Mol. Psychiatry 25, 2455–2467 (2020). PubMed PMC
Biological insights from 108 schizophrenia-associated genetic loci. Nature 511, 421–427 (2014). PubMed PMC
Räsänen S, Pakaslahti A, Syvälahti E, Jones PB & Isohanni M.Sex differences in schizophrenia: A review. Nord. J. Psychiatry 54, 37–45 (2000).
Zeng J.et al. Bayesian analysis of GWAS summary data reveals differential signatures of natural selection across human complex traits and functional genomic categories. bioRxiv 752527 (2019) doi:10.1101/752527. PubMed DOI PMC
Aguet F.et al. Genetic effects on gene expression across human tissues. Nature 550, 204–213 (2017). PubMed PMC
Genome-wide association study identifies five new schizophrenia loci. Nat. Genet 43, 969–978 (2011). PubMed PMC
Skene NG et al. Genetic identification of brain cell types underlying schizophrenia. Nat. Genet 50, 825–833 (2018). PubMed PMC
Habib N.et al. Massively parallel single-nucleus RNA-seq with DroNc-seq. Nat. Methods 14, 955–958 (2017). PubMed PMC
Zeisel A.et al. Molecular Architecture of the Mouse Nervous System. Cell 174, 999–1014.e22 (2018). PubMed PMC
Koopmans F.et al. SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse. Neuron 103, 217–234.e4 (2019). PubMed PMC
Benner C.et al. FINEMAP: Efficient variable selection using summary data from genome-wide association studies. Bioinformatics 32, 1493–1501 (2016). PubMed PMC
Sakuntabhai A.et al. Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease. Nat. Genet 21, 271–277 (1999). PubMed
Cederlöf M.et al. The association between Darier disease, bipolar disorder, and schizophrenia revisited: A population-based family study. Bipolar Disord. 17, 340–344 (2015). PubMed
Pardiñas AF et al. Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection. Nat. Genet 50, 381–389 (2018). PubMed PMC
Zhu Z.et al. Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets. Nat. Genet 48, 481–487 (2016). PubMed
Gandal MJ et al. Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder. Science (80-. ) 362, (2018). PubMed PMC
O’Brien HE et al. Expression quantitative trait loci in the developing human brain and their enrichment in neuropsychiatric disorders. Genome Biol. 19, 194 (2018). PubMed PMC
Võsa U.et al. Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression. Nat. Genet 53, 1300–1310 (2021). PubMed PMC
Wang D.et al. Comprehensive functional genomic resource and integrative model for the human brain. Science (80-. ) 362, eaat8464 (2018). PubMed PMC
Galvan L.et al. The Striatal Kinase DCLK3 Produces Neuroprotection Against Mutant Huntingtin - PubMed. Brain 141, 1434–1454 (2018). PubMed PMC
Rees E.et al. Analysis of intellectual disability copy number variants for association with schizophrenia. JAMA Psychiatry 73, 963–969 (2016). PubMed PMC
Fromer M.et al. De novo mutations in schizophrenia implicate synaptic networks. Nature 506, 179–184 (2014). PubMed PMC
Kaplanis J.et al. Integrating healthcare and research genetic data empowers the discovery of 49 novel developmental disorders. bioRxiv (2019) doi:10.1101/797787. DOI
Satterstrom FK et al. Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism. Cell 180, 568–584.e23 (2020). PubMed PMC
Luo Y.et al. Exploring the genetic architecture of inflammatory bowel disease by whole-genome sequencing identifies association at ADCY7. Nat. Genet 49, 186–192 (2017). PubMed PMC
Cheng Y.et al. Rare genetic variants affecting urine metabolite levels link population variation to inborn errors of metabolism. Nat. Commun 12, (2021). PubMed PMC
Singh T, Neale BM & Daly MJ Exome sequencing identifies rare coding variants in 10 genes which confer substantial risk for schizophrenia on behalf of the Schizophrenia Exome Meta-Analysis (SCHEMA) Consortium*. medRxiv 2020.09.18.20192815 (2020).
Priya A, Johar K.& Wong-Riley MTT Specificity protein 4 functionally regulates the transcription of NMDA receptor subunits GluN1, GluN2A, and GluN2B. Biochim. Biophys. Acta - Mol. Cell Res 1833, 2745–2756 (2013). PubMed PMC
Ripke S.et al. Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nat. Genet 45, 1150–1159 (2013). PubMed PMC
Kirov G.et al. De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia. Mol. Psychiatry 17, 142–153 (2012). PubMed PMC
Lek M.et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature 536, 285–291 (2016). PubMed PMC
Fagerberg L.et al. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol. Cell. Proteomics 13, 397–406 (2014). PubMed PMC
Biological insights from 108 schizophrenia-associated genetic loci. Nature 511, 421–427 (2014). PubMed PMC
Lam M.et al. Comparative genetic architectures of schizophrenia in East Asian and European populations. Nat. Genet (2019) doi:10.1038/s41588-019-0512-x. PubMed DOI PMC
Lam M.et al. RICOPILI: Rapid Imputation for COnsortias PIpeLIne. Bioinformatics (2019) doi:10.1093/bioinformatics/btz633. PubMed DOI PMC
Purcell S, Neale B, Todd-Brown K, Thomas L.& Ferreira MA PLINK: a toolset for whole-genome association and population-based linkage analysis. Am J Hum Genet 81, (2007). PubMed PMC
Devlin B.& Roeder K.Genomic Control for Association Studies. Biometrics 55, 997–1004 (1999). PubMed
Reference-based phasing using the Haplotype Reference Consortium panel. Nat. Genet 48, 1443–1448 (2016). PubMed PMC
Das S.et al. Next-generation genotype imputation service and methods. Nat. Genet 48, 1284–1287 (2016). PubMed PMC
Haplotype Reference Consortium r1.1. https://ega-archive.org/datasets/EGAD00001002729.
O’Connell J.et al. Haplotype estimation for biobank-scale data sets. Nat. Genet 48, 817–820 (2016). PubMed PMC
Bycroft C.et al. Genome-wide genetic data on ~500,000 UK Biobank participants. bioRxiv 166298 (2017) doi:10.1101/166298. DOI
Chang CC et al. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience 4, 7 (2015). PubMed PMC
Lee JJ et al. Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals. Nat. Genet 50, 1112–1121 (2018). PubMed PMC
Tukiainen T.et al. Landscape of X chromosome inactivation across human tissues. Nature 550, 244–248 (2017). PubMed PMC
Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460, 748–752 (2009). PubMed PMC
Vittinghoff E.& McCulloch CE Relaxing the rule of ten events per variable in logistic and cox regression. Am. J. Epidemiol 165, 710–718 (2007). PubMed
Heinze G.& Ploner M.A SAS macro, S-PLUS library and R package to perform logistic regression without convergence problems. https://cemsiis.meduniwien.ac.at/fileadmin/user_upload/_imported/fileadmin/msi_akim/CeMSIIS/KB/programme/tr2_2004.pdf (2004).
Viechtbauer W.Conducting Meta-Analyses in R with the metafor Package. J. Stat. Softw 36, 1–48 (2010).
Lee SH, Goddard ME, Wray NR & Visscher PM A Better Coefficient of Determination for Genetic Profile Analysis. Genet. Epidemiol 36, 214–224 (2012). PubMed
Martínez-Camblor P.Fully non-parametric receiver operating characteristic curve estimation for random-effects meta-analysis. Stat. Methods Med. Res 26, 5–20 (2017). PubMed
Bigdeli TB et al. Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry. Mol. Psychiatry 25, 2455–2467 (2020). PubMed PMC
Aguet F.et al. Genetic effects on gene expression across human tissues. Nature 550, 204–213 (2017). PubMed PMC
Habib N.et al. Massively parallel single-nucleus RNA-seq with DroNc-seq. Nat. Methods 14, 955–958 (2017). PubMed PMC
Skene NG et al. Genetic identification of brain cell types underlying schizophrenia. Nat. Genet 50, 825–833 (2018). PubMed PMC
Zeisel A.et al. Molecular Architecture of the Mouse Nervous System. Cell 174, 999–1014.e22 (2018). PubMed PMC
Bryois J.et al. Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease. Nat. Genet 1–12 (2020) doi:10.1038/s41588-020-0610-9. PubMed DOI PMC
de Leeuw CA, Mooij JM, Heskes T.& Posthuma D.MAGMA: Generalized Gene-Set Analysis of GWAS Data. PLOS Comput. Biol 11, e1004219 (2015). PubMed PMC
Finucane HK et al. Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types. Nat. Genet 50, 621–629 (2018). PubMed PMC
Durinck S, Spellman PT, Birney E.& Huber W.Mapping identifiers for the integration of genomic datasets with the R/ Bioconductor package biomaRt. Nat. Protoc 4, 1184–1191 (2009). PubMed PMC
Maston GA, Evans SK & Green MR Transcriptional Regulatory Elements in the Human Genome. Annu. Rev. Genomics Hum. Genet 7, 29–59 (2006). PubMed
A reference panel of 64,976 haplotypes for genotype imputation. Nat. Genet 48, 1279–1283 (2016). PubMed PMC
Koopmans F.et al. SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse. Neuron 103, 217–234.e4 (2019). PubMed PMC
Genovese G.et al. Increased burden of ultra-rare protein-altering variants among 4,877 individuals with schizophrenia. Nat. Neurosci 19, 1433–1441 (2016). PubMed PMC
Pardiñas AF et al. Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection. Nat. Genet 50, 381–389 (2018). PubMed PMC
Merico D, Isserlin R, Stueker O, Emili A.& Bader GD Enrichment Map: A Network-Based Method for Gene-Set Enrichment Visualization and Interpretation. PLoS One 5, e13984 (2010). PubMed PMC
Benner C.et al. FINEMAP: Efficient variable selection using summary data from genome-wide association studies. Bioinformatics 32, 1493–1501 (2016). PubMed PMC
Benner C.et al. Prospects of Fine-Mapping Trait-Associated Genomic Regions by Using Summary Statistics from Genome-wide Association Studies. Am. J. Hum. Genet 101, 539–551 (2017). PubMed PMC
Zhu Z.et al. Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets. Nat. Genet 48, 481–487 (2016). PubMed
O’Brien HE et al. Expression quantitative trait loci in the developing human brain and their enrichment in neuropsychiatric disorders. Genome Biol. 19, 194 (2018). PubMed PMC
Gandal MJ et al. Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder. Science (80-. ) 362, (2018). PubMed PMC
Võsa U.et al. Unraveling the polygenic architecture of complex traits using blood eQTL metaanalysis. bioRxiv 447367 (2018) doi:10.1101/447367. DOI
Sonnega A.et al. Cohort profile: The Health and Retirement Study (HRS). Int. J. Epidemiol 43, 576–585 (2014). PubMed PMC
Yang J, Lee SH, Goddard ME & Visscher PM GCTA: A Tool for Genome-wide Complex Trait Analysis. Am. J. Hum. Genet 88, 76–82 (2011). PubMed PMC
Yang J.et al. Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits. Nat. Genet 44, 369–375 (2012). PubMed PMC
Gusev A.et al. Integrative approaches for large-scale transcriptome-wide association studies. Nat. Genet 48, 245–252 (2016). PubMed PMC
Zhang W.et al. Integrative transcriptome imputation reveals tissue-specific and shared biological mechanisms mediating susceptibility to complex traits. Nat. Commun 10, (2019). PubMed PMC
Fine-mapping genomic loci refines bipolar disorder risk genes
Genomics yields biological and phenotypic insights into bipolar disorder
Fine-mapping genomic loci refines bipolar disorder risk genes