Downloads provided by UsageCountsMapping genomic loci implicates genes and synaptic biology in schizophrenia
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UKRI| A genome-wide association study of psychosis and its characteristic endophenotypes ,
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Vassily Trubetskoy; Antonio F. Pardiñas; Ting Qi; Georgia Panagiotaropoulou; Swapnil Awasthi; Tim B. Bigdeli; Julien Bryois; +193 Authors
Vassily Trubetskoy; Antonio F. Pardiñas; Ting Qi; Georgia Panagiotaropoulou; Swapnil Awasthi; Tim B. Bigdeli; Julien Bryois; Chia-Yen Chen; Charlotte A. Dennison; Lynsey S. Hall; Max Lam; Kyoko Watanabe; Oleksandr Frei; Tian Ge; Janet C. Harwood; Frank Koopmans; Sigurdur Magnusson; Alexander L. Richards; Julia Sidorenko; Yang Wu; Jian Zeng; Jakob Grove; Minsoo Kim; Zhiqiang Li; Georgios Voloudakis; Wen Zhang; Mark Adams; Ingrid Agartz; Elizabeth G. Atkinson; Esben Agerbo; Mariam Al Eissa; Margot Albus; Madeline Alexander; Behrooz Z. Alizadeh; Köksal Alptekin; Thomas D. Als; Farooq Amin; Volker Arolt; Manuel Arrojo; Lavinia Athanasiu; Maria Helena Azevedo; Silviu A. Bacanu; Nicholas J. Bass; Martin Begemann; Richard A. Belliveau; Judit Bene; Beben Benyamin; Sarah E. Bergen; Giuseppe Blasi; Julio Bobes; Stefano Bonassi; Alice Braun; Rodrigo Affonseca Bressan; Evelyn J. Bromet; Richard Bruggeman; Peter F. Buckley; Randy L. Buckner; Jonas Bybjerg-Grauholm; Wiepke Cahn; Murray J. Cairns; Monica E. Calkins; Vaughan J. Carr; David Castle; Stanley V. Catts; Kimberley D. Chambert; Raymond C. K. Chan; Boris Chaumette; Wei Cheng; Eric F. C. Cheung; Siow Ann Chong; David Cohen; Angèle Consoli; Quirino Cordeiro; Javier Costas; Charles Curtis; Michael Davidson; Kenneth L. Davis; Lieuwe de Haan; Franziska Degenhardt; Lynn E. DeLisi; Ditte Demontis; Faith Dickerson; Dimitris Dikeos; Timothy Dinan; Srdjan Djurovic; Jubao Duan; Giuseppe Ducci; Frank Dudbridge; Johan G. Eriksson; Lourdes Fañanás; Stephen V. Faraone; Alessia Fiorentino; Andreas Forstner; Josef Frank; Nelson B. Freimer; Menachem Fromer; Alessandra Frustaci; Ary Gadelha; Giulio Genovese; Elliot S. Gershon; Marianna Giannitelli; Ina Giegling; Paola Giusti-Rodríguez; Stephanie Godard; Jacqueline I. Goldstein; Javier González Peñas; Ana González-Pinto; Srihari Gopal; Jacob Gratten; Michael F. Green; Tiffany A. Greenwood; Olivier Guillin; Sinan Gülöksüz; Raquel E. Gur; Ruben C. Gur; Blanca Gutiérrez; Eric Hahn; Hakon Hakonarson; Vahram Haroutunian; Annette M. Hartmann; Carol Harvey; Caroline Hayward; Frans A. Henskens; Stefan Herms; Per Hoffmann; Daniel P. Howrigan; Masashi Ikeda; Conrad Iyegbe; Inge Joa; Antonio Julià; Anna K. Kähler; Tony Kam-Thong; Yoichiro Kamatani; Sena Karachanak-Yankova; Oussama Kebir; Matthew C. Keller; Brian J. Kelly; Andrey Khrunin; Sung-Wan Kim; Janis Klovins; Nikolay Kondratiev; Bettina Konte; Julia Kraft; Michiaki Kubo; Vaidutis Kučinskas; Zita Ausrele Kučinskiene; Agung Kusumawardhani; Hana Kuzelova-Ptackova; Stefano Landi; Laura C. Lazzeroni; Phil H. Lee; Sophie E. Legge; Douglas S. Lehrer; Rebecca Lencer; Bernard Lerer; Miaoxin Li; Jeffrey Lieberman; Gregory A. Light; Svetlana Limborska; Chih-Min Liu; Jouko Lönnqvist; Carmel M. Loughland; Jan Lubinski; Jurjen J. Luykx; Amy Lynham; Milan Macek; Andrew Mackinnon; Patrik K. E. Magnusson; Brion S. Maher; Wolfgang Maier; Dolores Malaspina; Jacques Mallet; Stephen R. Marder; Sara Marsal; Alicia R. Martin; Lourdes Martorell; Manuel Mattheisen; Robert W. McCarley; Colm McDonald; John J. McGrath; Helena Medeiros; Sandra Meier; Bela Melegh; Ingrid Melle; Raquelle I. Mesholam-Gately; Andres Metspalu; Patricia T. Michie; Lili Milani; Vihra Milanova; Marina Mitjans; Espen Molden; Esther Molina; María Dolores Molto; Valeria Mondelli; Carmen Moreno; Christopher P. Morley; Gerard Muntané; Kieran C. Murphy; Inez Myin-Germeys; Igor Nenadić;
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10261/272315 , 20.500.12530/111029 , 1871.1/c8f42a05-a3c7-4144-9db0-3f1d86d3342b , 11370/13756e62-6b2f-4eb9-8b02-4696a7ee7a38 , 20.500.14243/520398 , 11541.2/28911 , 21.11116/0000-000A-8E54-8 , 21.11116/0000-0010-D08D-4 , 21.11116/0000-0010-D08F-2 , 11562/1061683 , 10668/19569 , 11572/354015 , 11379/564760 , 2108/317018 , 11585/898943 , 11586/401848
Mapping genomic loci implicates genes and synaptic biology in schizophrenia
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.
United States, Poland, Germany, Italy, Netherlands, Italy, United Kingdom, Germany, Spain, Italy, Australia, United Kingdom, United Kingdom, Germany, Turkey, Denmark, Italy, Italy, Italy, Italy, United Kingdom, Greece, United Kingdom, Belgium, France
- University of Amsterdam Netherlands
- Lawrence Berkeley National Laboratory United States
- University of Brescia Italy
- Helmholtz Association of German Research Centres Germany
- University of California, Irvine United States
gene set enrichment analysis, Genetics of the nervous system, SynGO Consortium, Schizophrenia/genetics, genetic association, Integration, VARIANTS, heritability, DISEASE, Indonesia Schizophrenia Consortium, Architecture, inhibitory neuron, genetics, ontology, Aetiology, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Genetic Predisposition to Disease/genetics, Statistics, Variants, allele, ASSOCIATION, gene expression regulation, Genomics, STATISTICS, [SDV] Life Sciences [q-bio], nervous system function, Science & Technology - Other Topics, Profile, nerve cell, INTEGRATION, Single Nucleotide/genetics, Human, brain region, 610, Article, MYT1L gene, SDG 3 - Good Health and Well-being, excitatory neuron, Genetics, genomics, Humans, Alleles; Genetic Predisposition to Disease; Genomics; Humans; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Schizophrenia, human, Polymorphism, Psychosis Endophenotypes International Consortium, Alleles, neuropathology, Science & Technology, MUTATIONS, RERE gene, gene mapping, cell, schizophrenia, Polymorph, info:eu-repo/classification/ddc/500, PsychENCODE, Genome-wide association studies, CACNA1C gene, SLC39A8 gene, single nucleotide polymorphism, genetic variability, inglese, Settore BIO/13 - BIOLOGIA APPLICATA, 2.1 Biological and endogenous factors, Disease, gene mutation, neurotransmission, developmental disorder, Allele, RISK, ARCHITECTURE, Single Nucleotide, differentiation, Polymorphism, Single Nucleotide/genetics, Serious Mental Illness, neurologic disease, Multidisciplinary Sciences, receptor gene, comorbidity, Mental Health, FOXP1 gene, Mutations, Biotechnology, Risk, gene locus, General Science & Technology, PROFILE, genetic risk score, Polymorphism, Single Nucleotide, Association, GRIN2A gene, regulator gene, synaptic membrane, Genetic Predisposition to Disease, gene identification, genome-wide association study, nonhuman, Human Genome, BCL11B gene, disease association, Neurosciences, Individuals, gene structure, central nervous system, Brain Disorders, INDIVIDUALS, cell differentiation, FAM120A gene, SP4 gene, Genomic, Schizophrenia, Diseases of the nervous system, biological processes, genetic predisposition, Genome-Wide Association Study
gene set enrichment analysis, Genetics of the nervous system, SynGO Consortium, Schizophrenia/genetics, genetic association, Integration, VARIANTS, heritability, DISEASE, Indonesia Schizophrenia Consortium, Architecture, inhibitory neuron, genetics, ontology, Aetiology, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Genetic Predisposition to Disease/genetics, Statistics, Variants, allele, ASSOCIATION, gene expression regulation, Genomics, STATISTICS, [SDV] Life Sciences [q-bio], nervous system function, Science & Technology - Other Topics, Profile, nerve cell, INTEGRATION, Single Nucleotide/genetics, Human, brain region, 610, Article, MYT1L gene, SDG 3 - Good Health and Well-being, excitatory neuron, Genetics, genomics, Humans, Alleles; Genetic Predisposition to Disease; Genomics; Humans; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Schizophrenia, human, Polymorphism, Psychosis Endophenotypes International Consortium, Alleles, neuropathology, Science & Technology, MUTATIONS, RERE gene, gene mapping, cell, schizophrenia, Polymorph, info:eu-repo/classification/ddc/500, PsychENCODE, Genome-wide association studies, CACNA1C gene, SLC39A8 gene, single nucleotide polymorphism, genetic variability, inglese, Settore BIO/13 - BIOLOGIA APPLICATA, 2.1 Biological and endogenous factors, Disease, gene mutation, neurotransmission, developmental disorder, Allele, RISK, ARCHITECTURE, Single Nucleotide, differentiation, Polymorphism, Single Nucleotide/genetics, Serious Mental Illness, neurologic disease, Multidisciplinary Sciences, receptor gene, comorbidity, Mental Health, FOXP1 gene, Mutations, Biotechnology, Risk, gene locus, General Science & Technology, PROFILE, genetic risk score, Polymorphism, Single Nucleotide, Association, GRIN2A gene, regulator gene, synaptic membrane, Genetic Predisposition to Disease, gene identification, genome-wide association study, nonhuman, Human Genome, BCL11B gene, disease association, Neurosciences, Individuals, gene structure, central nervous system, Brain Disorders, INDIVIDUALS, cell differentiation, FAM120A gene, SP4 gene, Genomic, Schizophrenia, Diseases of the nervous system, biological processes, genetic predisposition, Genome-Wide Association Study
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