دورية أكاديمية
Interaction Testing and Polygenic Risk Scoring to Estimate the Association of Common Genetic Variants With Treatment Resistance in Schizophrenia
| العنوان: | Interaction Testing and Polygenic Risk Scoring to Estimate the Association of Common Genetic Variants With Treatment Resistance in Schizophrenia |
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| المؤلفون: | Pardiñas, Antonio F., Smart, Sophie E., Willcocks, Isabella R., Holmans, Peter A., Dennison, Charlotte A., Lynham, Amy J., Legge, Sophie E., Baune, Bernhard T., Bigdeli, Tim B., Cairns, Murray J., Corvin, Aiden, Fanous, Ayman H., Frank, Josef, Kelly, Brian, McQuillin, Andrew, Melle, Ingrid, Mortensen, Preben B., Mowry, Bryan J., Pato, Carlos N., Periyasamy, Sathish, Rietschel, Marcella, Rujescu, Dan, Simonsen, Carmen, St Clair, David, Tooney, Paul, Wu, Jing Qin, Andreassen, Ole A., Kowalec, Kaarina, Sullivan, Patrick F., Murray, Robin M., Owen, Michael J., MacCabe, James H., O’Donovan, Michael C., Walter, James, T., Homman, Lina |
| بيانات النشر: | Linköpings universitet, Avdelningen för Ã¥ldrande och social förändring Linköpings universitet, Avdelningen för funktionsnedsättning och samhälle Linköpings universitet, Filosofiska fakulteten MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom;Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom Department of Psychiatry, University of Münster, Münster, Germany;Department of Psychiatry, Melbourne Medical School, The University of Melbourne, Melbourne, Australia;The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Australia Department of Psychiatry and the Behavioral Sciences, State University of New York Downstate Medical Center, Brooklyn;Institute for Genomic Health, State University of New York Downstate Medical Center, Brooklyn;Department of Psychiatry, Veterans Affairs New York Harbor Healthcare System, Brooklyn School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, Australia;Centre for Brain and Mental Health Research, University of Newcastle, Newcastle, Australia;Hunter Medical Research Institute, Newcastle, Australia Neuropsychiatric Genetics Research Group, Department of Psychiatry, Trinity College Dublin, Dublin, Ireland Department of Psychiatry and the Behavioral Sciences, State University of New York Downstate Medical Center, Brooklyn;Institute for Genomic Health, State University of New York Downstate Medical Center, Brooklyn Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Mannheim, Germany School of Medicine & Public Health, The University of Newcastle, Newcastle, Australia Molecular Psychiatry Laboratory, Division of Psychiatry, University College London, London, United Kingdom Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway;Division of Mental Health and Addiction, Institute of Clinical Medicine, Oslo University Hospital, Oslo, Norway National Centre for Register-based Research, Aarhus University, Aarhus, Denmark;The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark Queensland Brain Institute, The University of Queensland, Brisbane, Australia;Queensland Centre for Mental Health Research, The University of Queensland, Brisbane, Australia Department of Psychiatry and Behavioral Sciences, State University of New York Downstate Medical Center, Brooklyn;Department of Psychiatry and Zilkha Neurogenetics Institute, Keck School of Medicine, University of Southern California, Los Angeles;Institute for Genomic Health, State University of New York Downstate Medical Center, Brooklyn University Clinic and Outpatient Clinic for Psychiatry, Psychotherapy and Psychosomatics, Martin Luther University of Halle-Wittenberg, Halle, Germany;Division of General Psychiatry, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway;Early Intervention in Psychosis Advisory Unit for South-East Norway, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, Australia;Hunter Medical Research Institute, Newcastle, Australia Baker Heart and Diabetes Institute, Melbourne, Australia College of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada;Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden;Department of Psychiatry, Icahn School of Medicine, Mount Sinai Hospital, New York, New York;Department of Genetics, University of North Carolina, Chapel Hill Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom Centre For Public Health, Institute Of Clinical Sciences, Queens University Belfast, Belfast, United Kingdom American Medical Association |
| سنة النشر: | 2022 |
| المجموعة: | Linköping University Electronic Press (LiU E-Press) |
| مصطلحات موضوعية: | Medical Genetics, Medicinsk genetik |
| الوصف: | Importance  About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts. Objective  To examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples. Design, Setting, and Participants  Two case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n = 10 501) and individuals with non-TRS (n = 20 325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G]). Main Outcomes and Measures  GWAS of treatment resistance in schizophrenia. The results of the GWAS were compared with complex polygenic traits through a genetic correlation approach and were used for PRS analysis on the independent validation cohorts using the same TRS definition. Results  The study included a total of 85 490 participants (48 635 [56.9%] male) in its GWAS stage and 1380 participants (859 [62.2%] ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | JAMA psychiatry, 2168-6238, 2022, 79:3, s. 260-269; orcid:0000-0002-5927-7050; http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-187809Test; PMID 35019943; ISI:000742416600002; Scopus 2-s2.0-85123016320 |
| DOI: | 10.1001/jamapsychiatry.2021.3799 |
| الإتاحة: | https://doi.org/10.1001/jamapsychiatry.2021.3799Test http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-187809Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.54735EF9 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1001/jamapsychiatry.2021.3799 |
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