ArticleNature genetics2026
Co-expression-based models improve eQTL predictions for transcriptome-wide association studies and highlight new schizophrenia-associated genes.
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Article in Nature genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
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Authors and funding
79 authors.
Fabiana RossiDepartment of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy.ORCID http://orcid.org/0009-0004-3724-9456
Leonardo SportelliDepartment of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy.
Gianluca C KikidisDepartment of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy.ORCID http://orcid.org/0009-0001-6979-7404
Giulia GrassiIMT School for Advanced Studies Lucca, Lucca, Italy.ORCID http://orcid.org/0009-0001-7816-668X
Fabio Di CamilloDepartment of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy.
Alessandro BertolinoDepartment of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy.
Giuseppe BlasiDepartment of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy.ORCID http://orcid.org/0000-0003-0878-1131
Christopher J BorcukDepartment of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy.
Daniela FuscoDepartment of Neurosciences "Rita Levi Montalcini", University of Turin, Turin, Italy.ORCID http://orcid.org/0009-0009-9062-571X
Thomas M HydeLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-8746-3037
Joel E KleinmanLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-4210-6052
Davide MarnettoDepartment of Neurosciences "Rita Levi Montalcini", University of Turin, Turin, Italy.ORCID http://orcid.org/0000-0001-9573-0601
Silvia PellegriniDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.ORCID http://orcid.org/0000-0003-0556-0165
Antonio RampinoDepartment of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy.ORCID http://orcid.org/0000-0002-9654-3266
Benedetto VitielloDepartment of Public Health and Pediatric Sciences, University of Turin, Turin, Italy.
Stephan RipkeDepartment of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin, Germany.ORCID http://orcid.org/0000-0003-3622-835X
Alice BraunDepartment of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin, Germany.
Julia KraftDepartment of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin, Germany.
Sintia Iole BelangeroDepartment of Morphology and Genetics, Laboratorio de Genetica, Universidade Federal de São Paulo, São Paulo, Brazil.ORCID http://orcid.org/0000-0002-2419-4351
Paulo R MenezesDepartment of Preventative Medicine, Faculdade de Medicina FMUSP, University of São Paulo, São Paulo, Brazil.
Celso ArangoHospital Universitario La Paz, IdiPAZ, School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.ORCID http://orcid.org/0000-0003-3382-4754
James T R WaltersCentre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.ORCID http://orcid.org/0000-0002-6980-4053
Michael C O'DonovanCentre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
Michael J OwenCentre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
David BraffDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Aiden CorvinNeuropsychiatric Genetics Research Group, Department of Psychiatry, Trinity College Dublin, Dublin, Ireland.ORCID http://orcid.org/0000-0001-6717-4089
Derek W MorrisCentre for Neuroimaging, Cognition and Genomics (NICOG), School of Biological and Chemical Sciences, University of Galway, Galway, Ireland.
Enrico DomeniciDepartment of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.ORCID http://orcid.org/0000-0001-7436-6919
Jim van OsUniversity Medical Center Utrecht, Department of Psychiatry, Utrecht, Netherlands.ORCID http://orcid.org/0000-0002-7245-1586
Esref AtbaşoğluDepartment of Psychiatry, School of Medicine, Ankara University, Ankara, Turkey.
Meram C SakaDepartment of Psychiatry, School of Medicine, Ankara University, Ankara, Turkey.
Marta Di FortiSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Bernhard T BauneDepartment of Psychiatry, University of Münster, Münster, Germany.
Carlos N PatoRutgers University, Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
Andrew McQuillinMolecular Psychiatry Laboratory, Division of Psychiatry, University College London, London, UK.ORCID http://orcid.org/0000-0003-1567-2240
Vera GolimbetRussian Mental Health Research Center, Moscow, Russia.
Nikolay KondratyevRussian Mental Health Research Center, Moscow, Russia.ORCID http://orcid.org/0000-0002-5134-6007
Valentina Escott-PriceCentre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.ORCID http://orcid.org/0000-0003-1784-5483
Anna GareevaBashkir State Medical University, Ufa, Russia.
Elza KhusnutdinovaBashkir State Medical University, Ufa, Russia.ORCID http://orcid.org/0000-0003-2987-3334
Jorge A CervillaDepartment of Psychiatry, San Cecilio University Hospital, University of Granada, Granada, Spain.ORCID http://orcid.org/0000-0001-6891-1992
Margarita RiveraDepartment of Biochemistry and Molecular Biology II, Faculty of Pharmacy, University of Granada, Granada, Spain.ORCID http://orcid.org/0000-0003-4717-1045
Dominique CampionINSERM, Rouen, France.
Claudine Laurent-LevinsonDepartment of Child and Adolescent Psychiatry, Reference Center for Rare Disease with Psychiatric Expression, Pitié-Salpêtrière University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.ORCID http://orcid.org/0000-0001-6550-3635
Alessandro SerrettiDepartment of Medicine and Surgery, Kore University of Enna, Enna, Italy.
Ole A AndreassenCentre for Precision Psychiatry, Division of Mental Health and Addiction, University of Oslo, Oslo, Norway.
David St ClairInstitute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
Todd LenczDivision of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USA.ORCID http://orcid.org/0000-0001-8586-338X
Anil K MalhotraDivision of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USA.
Nina S McCarthySchool of Biomedical Sciences, The University of Western Australia, Perth, Western Australia, Australia.
Bryan J MowryQueensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0002-4115-5645
Dan RujescuDepartment of Psychiatry and Psychotherapy, Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0002-1432-313X
Ina GieglingDepartment of Psychiatry and Psychotherapy, Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria.
Annette M HartmannDepartment of Psychiatry and Psychotherapy, Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria.
Bettina KonteDepartment of Psychiatry and Psychotherapy, Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0001-5287-308X
Markus M NöthenInstitute of Human Genetics, University of Bonn & University Hospital of Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0002-8770-2464
Marcella RietschelDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.ORCID http://orcid.org/0000-0002-5236-6149
George KirovCentre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
Patrick F SullivanDepartment of Genetics, University of North Carolina, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-6619-873X
Tracey L PetryshenPsychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Thomas WergeInstitute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, Copenhagen, Denmark.ORCID http://orcid.org/0000-0003-1829-0766
Andrew M McIntoshInstitute of Neuroscience and Cardiovascular Research, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-0198-4588
Tõnu EskoInstitute of Genomics, University of Tartu, Tartu, Estonia.
Erik G JönssonCentre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet and Stockholm Health Care Services, Stockholm Region, Stockholm, Sweden.ORCID http://orcid.org/0000-0001-8368-6332
Hannelore EhrenreichClinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
Brien P RileyVirginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
Douglas F LevinsonDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-8223-1301
Joseph D BuxbaumDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0001-8898-8313
Elvira BramonDivision of Psychiatry, Department of Mental Health Neuroscience, University College London, London, UK.ORCID http://orcid.org/0000-0003-1369-5983
Christina M HultmanDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Roel A OphoffCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.
Rolf AdolfssonDepartment of Clinical Sciences, Psychiatry, Umeå University, Umeå, Sweden.ORCID http://orcid.org/0000-0001-9785-8473
Eli A StahlDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Sinan GuloksuzDepartment of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0002-6626-1874
Bart P F RuttenDepartment of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands.ORCID http://orcid.org/0000-0002-9834-6346
Cristina M Del-BenNeuroscience and Behavior Department; Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
Florence ThibautUniversity Paris Cité, Hôpital Cochin-Tarnier, Paris, France.
Daniel R WeinbergerLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-2409-2969
Giulio PergolaDepartment of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy. giulio.pergola@libd.org.ORCID http://orcid.org/0000-0002-9193-1841
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most genetic variants associated with complex heritability phenotypes lie in non-coding regions and are thought to influence disease risk by regulating gene expression. However, most transcriptome-wide association approaches primarily model local (cis) genetic effects, leaving much of gene regulation unexplained. Here, we show that incorporating distal (trans) regulatory effects improves the prediction of gene expression and the identification of disease-associated genes. Using RNA sequencing data from six human post-mortem brain regions, we developed INGENE and MODULE, two models capturing the combined influence of candidate trans-acting variants within gene coexpression networks. Integrating these models with conventional cis-based predictors improved gene expression imputation (maximum likelihood estimation, α = 0.05) for 18,744 genes across regions. Applying this framework to Psychiatric Genomics Consortium wave 3 genotypes identified 766 genes associated with schizophrenia (P
Indexed as
Genetic Predisposition to DiseaseGenome-Wide Association StudyQuantitative Trait LociSchizophreniaTranscriptomeBrainGene Expression ProfilingGene Expression RegulationGene Regulatory NetworksGenotypeHumansModels, GeneticPhenotypePolymorphism, Single Nucleotide
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