Pharmacogenetics of antidepressant response: a polygenic approach
Pharmacogenetics of antidepressant response: a polygenic approach
Abstract BackgroundMajor depressive disorder (MDD) has a high personal and socio-economic burden and more than 60% of patients fail to achieve remission with the first antidepressant. The biological mechanisms behind antidepressant response are only partially known but genetic factors play a relevant role. A combined predictor across genetic variants may be useful to investigate this complex trait. MethodsPolygenic risk scores (PRS) were used to estimate multi-allelic contribution to: 1) antidepressant efficacy; 2) its overlap with MDD and schizophrenia. We constructed PRS and tested whether these predicted symptom improvement or remission from the GENDEP study (n=736) to the STAR*D study (n=1409) and vice-versa, including the whole sample or only patients treated with escitalopram or citalopram. Using summary statistics from Psychiatric Genomics Consortium for MDD and schizophrenia, we tested whether PRS from these disorders predicted symptom improvement in GENDEP, STAR*D, and five further studies (n=3756). ResultsNo significant prediction of antidepressant efficacy was obtained from PRS in GENDEP/STAR*D but this analysis might have been underpowered. There was no evidence of overlap in the genetics of antidepressant response with either MDD or schizophrenia, either in individual studies or a meta-analysis. Stratifying by antidepressant did not alter the results. DiscussionWe identified no significant predictive effect using PRS between pharmacogenetic studies. The genetic liability to MDD or schizophrenia did not predict response to antidepressants, suggesting differences between the genetic component of depression and treatment response. Larger or more homogeneous studies will be necessary to obtain a polygenic predictor of antidepressant response.
Kan Carol、Lewis Cathryn M.、Curtis Charles、O?ˉDonovan Michael、Wendland Jens R.、Perlis Roy、Arolt Volker、Domschke Katharina、Placentino Anna、Souery Daniel、?agar Tina、Czerski Piotr M.、Farmer Anne、Aitchison Katherine J.、Craig Ian、McGuffin Peter、Evans David、Buttensch?n Henriette N.、Schulze Thomas G.、Zobel Astrid、Newhouse Stephen、Fabbri Chiara、Garc¨aa-Gonz¨￠lez Judit、Tansey Katherine E.、Henigsberg Neven、Mors Ole、Kapur Shitij、Baune Bernhard T.、Giupponi Michel、Uher Rudolf、Hauser Joanna、Lewis Glyn、Peters Tim J.、Breen Gerome、Patel Hamel、Maier Wolfgang、Jerman Borut、Perroud Nader、Rietschel Marcella、Sang-Hyuk Lee、Major Depressive Disorder Working Group of the Psychiatric Genomic Consortium、Bondolfi Guido
Institute of Psychiatry, Psychology and NeuroscienceInstitute of Psychiatry, Psychology and NeuroscienceInstitute of Psychiatry, Psychology and NeuroscienceMedical Research Council Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff UniversityPharma Research and Early Development, F. Hoffmann¨CLa RocheDepartment of Psychiatry, Center for Experimental Drugs and Diagnostics, Massachusetts General HospitalDepartment of Psychiatry, University of M¨1nsterDepartment of Psychiatry Psychosomatics and Psychotherapy, University of WuerzburgBiological Psychiatry Unit and Dual Diagnosis Ward, Istituto Di Ricovero e Cura a Carattere Scientifico, Centro San Giovanni di DioLaboratoire de Psychologie M¨|dicale, Universit¨| Libre de Bruxelles and Psy Pluriel?a Centre Europ¨|en de Psychologie M¨|dicaleInstitute of Public Health of the Republic of SloveniaLaboratory of Psychiatric Genetics, Poznan University of Medical SciencesInstitute of Psychiatry, Psychology and NeuroscienceDepartment of Psychiatry, University of AlbertaInstitute of Psychiatry, Psychology and NeuroscienceInstitute of Psychiatry, Psychology and NeuroscienceMedical Research Council CAiTE Centre, School of Social and Community Medicine, University of BristolTranslational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus UniversityDivision of Genetic Epidemiology in Psychiatry, Central Institute of Mental HealthDepartment of Psychiatry, University of BonnInstitute of Psychiatry, Psychology and NeuroscienceInstitute of Psychiatry, Psychology and Neuroscience||Department of Biomedical and Neuromotor Sciences, University of BolognaInstitute of Psychiatry, Psychology and NeuroscienceCollege of Biomedical and Life Sciences, Cardiff UniversityCroatian Institute for Brain Research, Medical School, University of ZagrebPsychosis Research Unit, Aarhus University Hospital||The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH)Institute of Psychiatry, Psychology and NeuroscienceDiscipline of Psychiatry, School of Medicine, University of AdelaideDepartment of Genetic Medicine and Laboratories, University Hospitals of GenevaDepartment of Psychiatry, Dalhousie UniversityLaboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical SciencesDivision of Psychiatry, University College LondonSchool of Clinical Sciences, University of BristolInstitute of Psychiatry, Psychology and NeuroscienceInstitute of Psychiatry, Psychology and NeuroscienceDepartment of Psychiatry, University of BonnInstitute of Public Health of the Republic of Slovenia||Department of Molecular and Biomedical Sciences, Jozef Stefan InstituteDepartment of Psychiatry, University of GenevaDivision of Genetic Epidemiology in Psychiatry, Central Institute of Mental HealthInstitute of Psychiatry, Psychology and NeuroscienceFull list of Consortium members is given in Supplementary Materials S1Center of Excellence for Drug Discovery in Psychiatry, GlaxoSmithKline Medicines Research Centre
医药卫生理论医学研究方法神经病学、精神病学
antidepressantpharmacogenomicspolygenic risk scoresmajor depressive disorderschizophrenia
Kan Carol,Lewis Cathryn M.,Curtis Charles,O?ˉDonovan Michael,Wendland Jens R.,Perlis Roy,Arolt Volker,Domschke Katharina,Placentino Anna,Souery Daniel,?agar Tina,Czerski Piotr M.,Farmer Anne,Aitchison Katherine J.,Craig Ian,McGuffin Peter,Evans David,Buttensch?n Henriette N.,Schulze Thomas G.,Zobel Astrid,Newhouse Stephen,Fabbri Chiara,Garc¨aa-Gonz¨￠lez Judit,Tansey Katherine E.,Henigsberg Neven,Mors Ole,Kapur Shitij,Baune Bernhard T.,Giupponi Michel,Uher Rudolf,Hauser Joanna,Lewis Glyn,Peters Tim J.,Breen Gerome,Patel Hamel,Maier Wolfgang,Jerman Borut,Perroud Nader,Rietschel Marcella,Sang-Hyuk Lee,Major Depressive Disorder Working Group of the Psychiatric Genomic Consortium,Bondolfi Guido.Pharmacogenetics of antidepressant response: a polygenic approach[EB/OL].(2025-03-28)[2025-05-07].https://www.biorxiv.org/content/10.1101/093799.点此复制
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