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Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder
AT. Amare, A. Thalamuthu, KO. Schubert, JM. Fullerton, M. Ahmed, S. Hartmann, S. Papiol, U. Heilbronner, F. Degenhardt, F. Tekola-Ayele, L. Hou, YH. Hsu, T. Shekhtman, M. Adli, N. Akula, K. Akiyama, R. Ardau, B. Arias, JM. Aubry, R. Hasler, H....
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
Emerging Leadership Investigator Grant 2021 - 2008000
Department of Health | National Health and Medical Research Council (NHMRC)
NLK
ProQuest Central
od 2000-01-01 do Před 1 rokem
Open Access Digital Library
od 1997-01-01
Health & Medicine (ProQuest)
od 2000-01-01 do Před 1 rokem
Psychology Database (ProQuest)
od 2000-01-01 do Před 1 rokem
- MeSH
- acetylcholin metabolismus MeSH
- antimanika terapeutické užití farmakologie MeSH
- Bayesova věta MeSH
- bipolární porucha * farmakoterapie genetika MeSH
- celogenomová asociační studie metody MeSH
- dospělí MeSH
- jednonukleotidový polymorfismus genetika MeSH
- kohortové studie MeSH
- kyselina glutamová metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- lithium * terapeutické užití farmakologie MeSH
- multifaktoriální dědičnost * genetika MeSH
- sloučeniny lithia terapeutické užití farmakologie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P < 0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P = 9.8 × 10-12, R2 = 1.9%) and continuous (P = 6.4 × 10-9, R2 = 2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P = 3.9 × 10-4, R2 = 0.9%), but not for the continuous outcome (P = 0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
AMEOS Clinical Center Hildesheim Hildesheim Germany
Bipolar Center Wiener Neustadt Sigmund Freud University Medical Faculty Vienna Austria
Center for Molecular Medicine Karolinska University Hospital Stockholm Sweden
Center for Systems Neuroscience Hannover Germany
Centro de Investigación Biomédica en Salud Mental Instituto de Salud Carlos 3 Madrid Spain
Clinic for Psychiatry and Psychotherapy Clinical Center Werra Meißner Eschwege Germany
Department of Adult Psychiatry Poznan University of Medical Sciences Poznan Poland
Department of Biomedical Resonance University of Tuebingen Tuebingen Germany
Department of Biomedical Sciences University of Cagliari Cagliari Italy
Department of Biomedicine University Hospital Basel Basel Switzerland
Department of Clinical Neurosciences Karolinska Institutet Stockholm Sweden
Department of Clinical Psychiatry and Psychotherapy Brandenburg Medical School Brandenburg Germany
Department of General Psychiatry University of Tuebingen Tuebingen Germany
Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
Department of Mental Health Johns Hopkins Bloomberg School of Public Health Baltimore MD USA
Department of Molecular Medicine and Surgery Karolinska Institute Stockholm Sweden
Department of Pharmacology Dalhousie University Halifax NS Canada
Department of Psychiatry 2 Ulm University Bezirkskrankenhaus Günzburg Günzburg Germany
Department of Psychiatry and Behavioral Sciences Johns Hopkins University Baltimore MD USA
Department of Psychiatry and Psychology Mayo Clinic Rochester MN USA
Department of Psychiatry and Psychotherapy Agaplesion Diakonieklinikum Rotenburg Germany
Department of Psychiatry and Psychotherapy Bezirkskrankenhaus Augsburg Augsburg Germany
Department of Psychiatry and Psychotherapy Medical University of Vienna Vienna Austria
Department of Psychiatry and Psychotherapy Mental Health Institute Berlin Berlin Germany
Department of Psychiatry and Psychotherapy Philipps University Marburg Marburg Germany
Department of Psychiatry and Psychotherapy University Medical Center Göttingen Göttingen Germany
Department of Psychiatry and Psychotherapy University of Münster Münster Germany
Department of Psychiatry Dalhousie University Halifax Nova Scotia Canada
Department of Psychiatry Dokkyo Medical University School of Medicine Mibu Tochigi Japan
Department of Psychiatry Health North Hospital Group Bremen Germany
Department of Psychiatry Hokkaido University Graduate School of Medicine Sapporo Japan
Department of Psychiatry Lindner Center of Hope University of Cincinnati Mason OH USA
Department of Psychiatry Melbourne Medical School University of Melbourne Parkville VIC Australia
Department of Psychiatry Mood Disorders Unit HUG Geneva University Hospitals Geneva Switzerland
Department of Psychiatry Ruhr University Bochum LWL University Hospital Bochum Germany
Department of Psychiatry University of California San Diego San Diego CA USA
Department of Psychiatry University of Campania Luigi Vanvitelli Naples Italy
Department of Psychiatry University of Perugia Perugia Italy
Department of Psychiatry VA San Diego Healthcare System San Diego CA USA
Department of Quantitative Health Sciences Mayo Clinic Rochester MN USA
Discipline of Psychiatry School of Medicine University of Adelaide Adelaide SA Australia
Douglas Mental Health University Institute McGill University Montreal Canada
German Center for Neurodegenerative Diseases Göttingen Germany
HSL Institute for Aging Research Harvard Medical School Boston MA USA
Inserm U955 Translational Psychiatry laboratory Fondation FondaMental Créteil France
Institut de Biomedicina de la Universitat de Barcelona Barcelona Spain
Institute for Medical Informatics University Medical Center Göttingen Göttingen Germany
Institute for Translational Psychiatry University of Münster Münster Germany
Institute of Neuroscience and Medicine Research Center Jülich Jülich Germany
Institute of Psychiatric Phenomics and Genomics University Hospital LMU Munich Munich Germany
Karl Jaspers Clinic European Medical School Oldenburg Groningen Oldenburg 26160 Germany
Laboratory for Molecular Dynamics of Mental Disorders RIKEN Brain Science Institute Saitama Japan
Laboratory of Neuroscience Institute of Psychiatry University of Sao Paulo São Paulo Brazil
Max Planck Institute of Psychiatry Munich Germany
Mental Health Research Group IMIM Hospital del Mar Barcelona Catalonia Spain
Montreal Neurological Institute and Hospital McGill University Montreal Canada
Mood Disorders Center of Ottawa Ontario Canada
National Institute of Mental Health Klecany Czech Republic
Neuroscience Research Australia Sydney NSW Australia
Northern Adelaide Local Health Network Mental Health Services Adelaide SA Australia
Office of Mental Health VA San Diego Healthcare System San Diego CA USA
Pôle de Psychiatrie Générale Universitaire Hôpital Charles Perrens Bordeaux France
Program for Quantitative Genomics Harvard School of Public Health Boston MA USA
Psychiatric Genetic Unit Poznan University of Medical Sciences Poznan Poland
Psychiatrieverbund Oldenburger Land gGmbH Karl Jaspers Klinik Bad Zwischenahn Germany
School of Medical Sciences University of New South Wales Sydney NSW Australia
School of Psychiatry University of New South Wales and Black Dog Institute Sydney Australia
The Neuromodulation Unit McGill University Health Centre Montreal Canada
Unit of Clinical Pharmacology Hospital University Agency of Cagliari Cagliari Italy
Unitat de Zoologia i Antropologia Biològica University of Barcelona CIBERSAM Barcelona Spain
Citace poskytuje Crossref.org
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- $a Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder / $c AT. Amare, A. Thalamuthu, KO. Schubert, JM. Fullerton, M. Ahmed, S. Hartmann, S. Papiol, U. Heilbronner, F. Degenhardt, F. Tekola-Ayele, L. Hou, YH. Hsu, T. Shekhtman, M. Adli, N. Akula, K. Akiyama, R. Ardau, B. Arias, JM. Aubry, R. Hasler, H. Richard-Lepouriel, N. Perroud, L. Backlund, AK. Bhattacharjee, F. Bellivier, A. Benabarre, S. Bengesser, JM. Biernacka, A. Birner, C. Marie-Claire, P. Cervantes, HC. Chen, C. Chillotti, S. Cichon, C. Cruceanu, PM. Czerski, N. Dalkner, M. Del Zompo, JR. DePaulo, B. Étain, S. Jamain, P. Falkai, AJ. Forstner, L. Frisen, MA. Frye, S. Gard, JS. Garnham, FS. Goes, M. Grigoroiu-Serbanescu, AJ. Fallgatter, S. Stegmaier, T. Ethofer, S. Biere, K. Petrova, C. Schuster, K. Adorjan, M. Budde, M. Heilbronner, JL. Kalman, MO. Kohshour, D. Reich-Erkelenz, SK. Schaupp, EC. Schulte, F. Senner, T. Vogl, IG. Anghelescu, V. Arolt, U. Dannlowski, D. Dietrich, C. Figge, M. Jäger, FU. Lang, G. Juckel, C. Konrad, J. Reimer, M. Schmauß, A. Schmitt, C. Spitzer, M. von Hagen, J. Wiltfang, J. Zimmermann, TFM. Andlauer, A. Fischer, F. Bermpohl, P. Ritter, S. Matura, A. Gryaznova, I. Falkenberg, C. Yildiz, T. Kircher, J. Schmidt, M. Koch, K. Gade, S. Trost, IS. Haussleiter, M. Lambert, AC. Rohenkohl, V. Kraft, P. Grof, R. Hashimoto, J. Hauser, S. Herms, P. Hoffmann, E. Jiménez, JP. Kahn, L. Kassem, PH. Kuo, T. Kato, J. Kelsoe, S. Kittel-Schneider, E. Ferensztajn-Rochowiak, B. König, I. Kusumi, G. Laje, M. Landén, C. Lavebratt, M. Leboyer, SG. Leckband, A. Tortorella, M. Manchia, L. Martinsson, MJ. McCarthy, S. McElroy, F. Colom, V. Millischer, M. Mitjans, FM. Mondimore, P. Monteleone, CM. Nievergelt, MM. Nöthen, T. Novák, C. O'Donovan, N. Ozaki, A. Pfennig, C. Pisanu, JB. Potash, A. Reif, E. Reininghaus, GA. Rouleau, JK. Rybakowski, M. Schalling, PR. Schofield, BW. Schweizer, G. Severino, PD. Shilling, K. Shimoda, C. Simhandl, CM. Slaney, A. Squassina, T. Stamm, P. Stopkova, M. Maj, G. Turecki, E. Vieta, J. Veeh, SH. Witt, A. Wright, PP. Zandi, PB. Mitchell, M. Bauer, M. Alda, M. Rietschel, FJ. McMahon, TG. Schulze, SR. Clark, BT. Baune
- 520 9_
- $a Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P < 0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P = 9.8 × 10-12, R2 = 1.9%) and continuous (P = 6.4 × 10-9, R2 = 2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P = 3.9 × 10-4, R2 = 0.9%), but not for the continuous outcome (P = 0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a von Hagen, Martin $u Clinic for Psychiatry and Psychotherapy, Clinical Center Werra-Meißner, Eschwege, Germany
- 700 1_
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- 700 1_
- $a Zimmermann, Jörg $u Psychiatrieverbund Oldenburger Land gGmbH, Karl-Jaspers-Klinik, Bad Zwischenahn, Germany
- 700 1_
- $a Andlauer, Till F M $u Department of Neurology, University Hospital rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany $1 https://orcid.org/0000000229175889
- 700 1_
- $a Fischer, Andre $u German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Gryaznova, Anna $u Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Hoffmann, Per $u Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany $u Department of Biomedicine, University Hospital Basel, Basel, Switzerland
- 700 1_
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- 700 1_
- $a Kahn, Jean-Pierre $u Service de Psychiatrie et Psychologie Clinique, Centre Psychothérapique de Nancy - Université de Lorraine, Nancy, France
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Simhandl, Christian $u Bipolar Center Wiener Neustadt, Sigmund Freud University, Medical Faculty, Vienna, Austria
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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