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Publisher Correction: Gene expression imputation across multiple brain regions provides insights into schizophrenia risk.
In the HTML version of the article originally published, the author group 'The Schizophrenia Working Group of the Psychiatric Genomics Consortium' was displayed incorrectly. The error has been corrected in the HTML version of the article
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Gene expression imputation across multiple brain regions provides insights into schizophrenia risk.
Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression
Gene expression imputation across multiple brain regions provides insights into schizophrenia risk
Abstract
Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression.Working Group
The Schizophrenia Working Group of the Psychiatric Genomics Consortium
Stephan Ripke37,38
Benjamin M. Neale37,38,39,40
Aiden Corvin41
James T. R. Walters6
Kai-How Farh37
Peter A. Holmans6,42
Phil Lee37,38,40
Brendan Bulik-Sullivan37,38
David A. Collier43,44
Hailiang Huang37,39
Tune H. Pers39,45,46
Ingrid Agartz47,48,49
Esben Agerbo8,32,33
Margot Albus50
Madeline Alexander51
Farooq Amin52,53
Silviu A. Bacanu54
Martin Begemann55
Richard A. Belliveau Jr38
Judit Bene56,57
Sarah E. Bergen38,58
Elizabeth Bevilacqua38
Tim B. Bigdeli54
Donald W. Black59
Richard Bruggeman60
Nancy G. Buccola61
Randy L. Buckner62,63,64
William Byerley65
Wiepke Cahn66
Guiqing Cai2,3
Dominique Campion67
Rita M. Cantor10
Vaughan J. Carr68,69
Noa Carrera6
Stanley V. Catts68,70
Kimberly D. Chambert38
Raymond C. K. Chan71
Ronald Y. L. Chen72
Eric Y. H. Chen72,73
Wei Cheng15
Eric F. C. Cheung74
Siow Ann Chong75
C. Robert Cloninger76
David Cohen77
Nadine Cohen78
Paul Cormican41
Nick Craddock6,42
James J. Crowley79
David Curtis80,81
Michael Davidson82
Kenneth L. Davis3
Franziska Degenhardt83,84
Jurgen Del Favero85
Ditte Demontis7,8,9
Dimitris Dikeos86
Timothy Dinan87
Srdjan Djurovic49,88
Gary Donohoe41,89
Elodie Drapeau3
Jubao Duan90,91
Frank Dudbridge92
Naser Durmishi93
Peter Eichhammer94
Johan Eriksson95,96,97
Valentina Escott-Price6
Laurent Essioux98
Ayman H. Fanous99,100,101,102
Martilias S. Farrell79
Josef Frank103
Lude Franke104
Robert Freedman105
Nelson B. Freimer106
Marion Friedl107
Joseph I. Friedman3
Menachem Fromer1,37,38,40
Giulio Genovese38
Lyudmila Georgieva6
Ina Giegling107,108
Paola Giusti-RodrĂguez79
Stephanie Godard109
Jacqueline I. Goldstein37,39
Vera Golimbet110
Srihari Gopal111
Jacob Gratten112
Lieuwe de Haan113
Christian Hammer55
Marian L. Hamshere6
Mark Hansen114
Thomas Hansen8,30
Vahram Haroutunian3,25,23
Annette M. Hartmann107
Frans A. Henskens68,115,116
Stefan Herms83,84,117
Joel N. Hirschhorn39,46,118
Per Hoffmann83,84,117
Andrea Hofman83,84
Mads V. Hollegaard36
David M. Hougaard36
Masashi Ikeda119
Inge Joa120
Antonio Julia121
Rene S. Kahn66
Luba Kalaydjieva122,123
Sena Karachanak-Yankova124
Juha Karjalainen104
David Kavanagh6
Matthew C. Keller125
James L. Kennedy126,127,128
Andrey Khrunin129
Yunjung Kim79
Janis Klovins130
James A. Knowles131
Bettina Konte107
Vaidutis Kucinskas132
Zita Ausrele Kucinskiene132
Hana Kuzelova-Ptackova133
Anna K. Kahler58
Claudine Laurent51,134
Jimmy Lee Chee Keong75,135
S. Hong Lee112
Sophie E. Legge6
Bernard Lerer136
Miaoxin Li72,73,137
Tao Li138
Kung-Yee Liang139
Jeffrey Lieberman140
Svetlana Limborska129
Carmel M. Loughland68,141
Jan Lubinski142
Jouko Lonnqvist143
Milan Macek Jr133
Patrik K. E. Magnusson58
Brion S. Maher144
Wolfgang Maier145
Jacques Mallet146
Sara Marsal121
Manuel Mattheisen7,8,9,147
Morten Mattingsdal49,148
Robert W. McCarley149,150
Colm McDonald151
Andrew M. McIntosh152,153
Sandra Meier103
Carin J. Meijer113
Bela Melegh56,57
Ingrid Melle49,154
Raquelle I. Mesholam-Gately149,155
Andres Metspalu156
Patricia T. Michie68,157
Lili Milani156
Vihra Milanova158
Younes Mokrab43
Derek W. Morris41,89
Ole Mors8,9,159
Kieran C. Murphy160
Robin M. Murray161
Inez Myin-Germeys162
Bertram Muller-Myhsok163,164,165
Mari Nelis156
Igor Nenadic166
Deborah A. Nertney167
Gerald Nestadt168
Kristin K. Nicodemus169
Liene Nikitina-Zake130
Laura Nisenbaum170
Annelie Nordin171
Eadbhard OâCallaghan172
Colm OâDushlaine38
F. Anthony OâNeill173
Sang-Yun Oh174
Ann Olincy126
Line Olsen8,64
Jim Van Os162,175
Christos Pantelis68,176
George N. Papadimitriou86
Sergi Papiol55
Elena Parkhomenko3
Michele T. Pato131
Tiina Paunio177,178
Milica Pejovic-Milovancevic179
Diana O. Perkins180
Olli PietilÀinen178,181
Jonathan Pimm81
Andrew J. Pocklington6
John Powell161
Alkes Price39,182
Ann E. Pulver168
Shaun M. Purcell1
Digby Quested183
Henrik B. Rasmussen30,43
Abraham Reichenberg3
Mark A. Reimers184
Alexander L. Richards6
Joshua L. Roffman62,64
Panos Roussos1,4
Douglas M. Ruderfer1,5,6
Veikko Salomaa97
Alan R. Sanders90,91
Ulrich Schall68,141
Christian R. Schubert185
Thomas G. Schulze103,186
Sibylle G. Schwab187
Edward M. Scolnick38
Rodney J. Scott68,188,189
Larry J. Seidman144,155
Jianxin Shi190
Engilbert Sigurdsson191
Teimuraz Silagadze192
Jeremy M. Silverman3,193
Kang Sim75
Petr Slominsky129
Jordan W. Smoller38,40
Hon-Cheong So72
Chris C. A. Spencer194
Eli A. Stahl1,2,3,4
Hreinn Stefansson195
Stacy Steinberg195
Elisabeth Stogmann196
Richard E. Straub197
Eric Strengman66,198
Jana Strohmaier103
T. Scott Stroup140
Mythily Subramaniam75
Jaana Suvisaari143
Dragan M. Svrakic76
Jin P. Szatkiewicz79
Erik Soderman47
Srinivas Thirumalai199
Draga Toncheva124
Sarah Tosato200
Juha Veijola201,202
John Waddington203
Dermot Walsh204
Dai Wang111
Qiang Wang138
Bradley T. Webb54
Mark Weiser82
Dieter B. Wildenauer205
Nigel M. Williams6
Stephanie Williams79
Stephanie H. Witt103
Aaron R. Wolen184
Emily H. M. Wong72
Brandon K. Wormley54
Hualin Simon Xi206
Clement C. Zai126,127
Xuebin Zheng207
Fritz Zimprich196
Naomi R. Wray112
Kari Stefansson195
Peter M. Visscher112
Rolf Adolfsson171
Ole A. Andreassen49,154
Douglas H. R. Blackwood153
Elvira Bramon208
Joseph D. Buxbaum2,3,24,25
Anders D. BĂžrglum7,8,9,159
Sven Cichon83,84,117,209
Ariel Darvasi210
Enrico Domenici211
Hannelore Ehrenreich55
Tonu Esko39,46,118,156
Pablo V. Gejman90,91
Michael Gill41
Hugh Gurling81
Christina M. Hultman58
Nakao Iwata119
Assen V. Jablensky68,123,205,212
Erik G. Jonsson47,49
Kenneth S. Kendler213
George Kirov6
Jo Knight125,127,128
Todd Lencz214,215,216
Douglas F. Levinson51
Qingqin S. Li111
Jianjun Liu207,217
Anil K. Malhotra214,215,216
Steven A. McCarroll38,118
Andrew McQuillin81
Jennifer L. Moran38
Preben B. Mortensen8,32,33
Bryan J. Mowry112,218
Markus M. Nothen83,84
Roel A. Ophoff10,66,105
Michael J. Owen6,42
Aarno Palotie38,40,181
Carlos N. Pato131
Tracey L. Petryshen38,149,219
Danielle Posthuma220,221,222
Marcella Rietschel103
Brien P. Riley213
Dan Rujescu107,108
Pak C. Sham72,73,137
Pamela Sklar1,2,3,4,25
David St Clair223
Daniel R. Weinberger197,224
Jens R. Wendland185
Thomas Werge8,30,225
Mark J. Daly37,38,39
Patrick F. Sullivan58,79,180
Michael C. OâDonovan6,42
20Integrated Technology Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Fujisawa, Japan.
21Neuropsychiatry Section, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
22Neuropsychiatric Signaling Program, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
23Psychiatry, JJ Peters Virginia Medical Center, Bronx, NY, USA.
24Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, NY, USA.
25Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
26Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
27CNS Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Fujisawa, Japan.
28F. Hoffman-La Roche Ltd, Basel, Switzerland.
29Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark.
30Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
31Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
32National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark.
33Centre for Integrated Registerbased Research, Aarhus University, Aarhus, Denmark.
34Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark.
35Mental Health Services in the Capital Region of Denmark, Mental Health Center Copenhagen, University of Copenhagen, Copenhagen, Denmark.
36Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
37Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
38Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
39Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
40Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
41Neuropsychiatric Genetics Research Group, Department of Psychiatry, Trinity College Dublin, Dublin, Ireland.
42NationalCentre for Mental Health, Cardiff University, Cardiff, UK.
43Eli Lilly and Company Limited, Erl Wood Manor, Sunninghill Road, Windlesham, Surrey, UK.
44Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Kingâs College London, London, UK.
45Center for BiologicalSequence Analysis, Department of Systems Biology, Technical University of Denmark, Kongens Lyngby, Denmark.
46Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Childrenâs Hospital, Boston, MA, USA.
47Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm, Sweden.
48Department of Psychiatry, Diakonhjemmet Hospital, Oslo, Norway.
49NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
50State Mental Hospital, Haar, Germany.
51Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
52Department of Psychiatry and Behavioral Sciences, Atlanta Veterans Affairs Medical Center, Atlanta, GA, USA.
53Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA.
54Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
55Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Gottingen, Germany.
56Department of Medical Genetics, University of PĂ©cs, PĂ©cs, Hungary.
57Szentagothai Research Center, University of PĂ©cs, PĂ©cs, Hungary.
58Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
59Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
60University Medical Center Groningen, Department of Psychiatry, University of Groningen, Groningen, the Netherlands.
61School of Nursing, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
62Athinoula A. Martinos Center, Massachusetts General Hospital, Boston, MA, USA.
63Center for Brain Science, Harvard University, Cambridge, MA, USA.
64Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
65Department of Psychiatry, University of California at San Francisco, San Francisco, CA, USA.
66University Medical Center Utrecht, Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, Utrecht, the Netherlands.
67Centre Hospitalier du Rouvray and INSERM U1079 Faculty of Medicine, Rouen, France.
68Schizophrenia Research Institute, Sydney, New South Wales, Australia.
69School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia.
70Royal Brisbane and Womenâs Hospital, University of Queensland, Brisbane, Queensland, Australia.
71Institute of Psychology, Chinese Academy of Science, Beijing, China.
72Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
73State Key Laboratory for Brain and Cognitive Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
74Castle Peak Hospital, Hong Kong, China.
75Institute of Mental Health, Singapore, Singapore.
76Department of Psychiatry, Washington University, St. Louis, MO, USA.
77Department of Child and Adolescent Psychiatry, Assistance Publique Hopitaux de Paris, Pierre and Marie Curie Faculty of Medicine and Institute for Intelligent Systems and Robotics, Paris, France.
78Blue Note Biosciences, Princeton, NJ, USA.
79Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
80Department of Psychological Medicine, Queen Mary University of London, London, UK.
81Molecular Psychiatry Laboratory, Division of Psychiatry, University College London, London, UK.
82Sheba Medical Center, Tel Hashomer, Israel.
83Department of Genomics, Life and Brain Center, Bonn, Germany.
84Institute of Human Genetics, University of Bonn, Bonn, Germany.
85AppliedMolecular Genomics Unit, VIB Department of Molecular Genetics, University of Antwerp, Antwerp, Belgium.
86First Department of Psychiatry, University of Athens Medical School, Athens, Greece.
87Department of Psychiatry, University College Cork, Co, Cork, Ireland.
88Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
89Cognitive Genetics and Therapy Group, School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Co, Galway, Ireland.
90Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
91Department of Psychiatry and Behavioral Sciences, North Shore University Health System, Evanston, IL, USA.
92Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
93Department of Child and Adolescent Psychiatry, University Clinic of Psychiatry, Skopje, Republic of Macedonia.
94Department of Psychiatry, University of Regensburg, Regensburg, Germany.
95Department of General Practice, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
96FolkhÀlsan Research Center, Helsinki, Finland, Biomedicum Helsinki, Helsinki, Finland.
97National Institute for Health and Welfare, Helsinki, Finland.
98Translational Technologies and Bioinformatics, Pharma Research and Early Development, F. Hoffman-La Roche, Basel, Switzerland.
99Department of Psychiatry, Georgetown University School of Medicine, Washington, DC, USA.
100Department of Psychiatry, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
101Department of Psychiatry, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
102Mental Health Service Line, Washington VA Medical Center, Washington, DC, USA.
103Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Mannheim, Germany.
104Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.
105Department of Psychiatry, University of Colorado Denver, Aurora, CO, USA.
106Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA.
107Department of Psychiatry, University of Halle, Halle, Germany.
108Department of Psychiatry, University of Munich, Munich, Germany.
109Departments of Psychiatry and Human and Molecular Genetics, INSERM, Institut de Myologie, HĂŽpital de la PitiĂš-SalpĂȘtriĂšre, Paris, France.
110Mental Health Research Centre, Russian Academy of Medical Sciences, Moscow, Russia.
111Neuroscience Therapeutic Area, Janssen Research and Development, Raritan, NJ, USA.
112Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
113Academic Medical Centre University of Amsterdam, Department of Psychiatry, Amsterdam, the Netherlands.
114Illumina, La Jolla, CA, USA.
115Priority Research Centre for Health Behaviour, University of Newcastle, Newcastle, New South Wales, Australia.
116School of Electrical Engineering and Computer Science, University of Newcastle, Newcastle, New South Wales, Australia.
117Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland.
118Department of Genetics, Harvard Medical School, Boston, MA, USA.
119Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan.
120Regional Centre for Clinical Researchin Psychosis, Department of Psychiatry, Stavanger University Hospital, Stavanger, Norway.
121Rheumatology Research Group, Vall dâHebron Research Institute, Barcelona, Spain.
122Centre for Medical Research, The University of Western Australia, Perth, Western Australia, Australia.
123The Perkins Institute for Medical Research, The University of Western Australia, Perth, Western Australia, Australia.
124Department of Medical Genetics, Medical University, Sofia, Bulgaria.
125Department of Psychology, University of Colorado Boulder, Boulder, CO, USA.
126Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
127Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
128Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
129Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russia.
130Latvian Biomedical Research and Study Centre, Riga, Latvia.
131Department of Psychiatry and Zilkha Neurogenetics Institute, Keck School of Medicine at University of Southern California, Los Angeles, CA, USA.
132Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
133Department of Biology and Medical Genetics, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
134Department of Child and Adolescent Psychiatry, Pierre and Marie Curie Faculty of Medicine, Paris, France.
135Duke-NUS Graduate Medical School, Singapore, Singapore.
136Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
137Centre for Genomic Sciences, The University of Hong Kong, Hong Kong, China.
138Mental Health Centre and Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
139Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
140Department of Psychiatry, Columbia University, New York, New York, NY, USA.
141Priority Centre for Translational Neuroscience and Mental Health, University of Newcastle, Newcastle, New South Wales, Australia.
142Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, Szczecin, Poland.
143Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland.
144Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
145Department of Psychiatry, University of Bonn, Bonn, Germany.
146Centre National de la Recherche Scientifique, Laboratoire de GĂ©nĂ©tique MolĂ©culaire de la Neurotransmission et des Processus NeurodĂ©nĂ©gĂ©ratifs, HĂŽpital de la PitiĂš-SalpĂȘtriĂšre, Paris, France.
147Department of Genomics Mathematics, University of Bonn, Bonn, Germany.
148Research Unit, SĂžrlandet Hospital, Kristiansand, Norway.
149Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
150VA Boston Health Care System, Brockton, MA, USA.
151Department of Psychiatry, National University of Ireland Galway, Co, Galway, Ireland.
152Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
153Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
154Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
155Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Boston, MA, USA.
156Estonian Genome Center, University of Tartu, Tartu, Estonia.
157School of Psychology, University of Newcastle, Newcastle, New South Wales, Australia.
158First Psychiatric Clinic, Medical University, Sofia, Bulgaria.
159Department P, Aarhus University Hospital, Risskov, Denmark.
160Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland.
161Kingâs College London, London, UK.
162Maastricht University Medical Centre, South Limburg Mental Health Research and TeachingNetwork, EURON, Maastricht, the Netherlands.
163Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
164Max Planck Institute of Psychiatry, Munich, Germany.
165Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
166Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.
167Department of Psychiatry, Queensland Brain Institute and Queensland Centre for Mental Health Research, University of Queensland, Brisbane, Queensland, Australia.
168Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
169Department of Psychiatry, Trinity College Dublin, Dublin, Ireland.
170Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA.
171Department of Clinical Sciences, Psychiatry, UmeÄ University, UmeÄ, Sweden.
172DETECT Early Intervention Service for Psychosis, Blackrock, Co, Dublin, Ireland.
173Centre for Public Health, Institute of Clinical Sciences, Queenâs University Belfast,
Gene expression imputation across multiple brain regions provides insights into schizophrenia risk
Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression.</p