269348 20260212164259.0 journal VDB UNRESTRICTED I:(DE-2719)1410006 I:(DE-2719)1410002 FullTexts DRIVER article DataCite Output Types/Journal article PUB:(DE-HGF)16 PUB:(DE-HGF) Journal Article journal journal 1715674675_2123 BibTeX ARTICLE ORCID JOURNAL_ARTICLE 0 EndNote Journal Article Thalamuthu, Anbupalam 1 0000-0003-1690-0209 Schubert, Klaus Oliver 2 0000-0003-4014-4490 Fullerton, Janice M 3 Ahmed, Muktar 4 0000-0001-9689-0594 Hartmann, Simon 5 0000-0001-9366-8728 Papiol, Sergi 6 P:(DE-2719)9000977 Heilbronner, Urs 7 Degenhardt, Franziska 8 Tekola-Ayele, Fasil 9 Hou, Liping 10 Hsu, Yi-Hsiang 11 Shekhtman, Tatyana 12 Adli, Mazda 13 Akula, Nirmala 14 Akiyama, Kazufumi 15 Ardau, Raffaella 16 0000-0001-9181-2132 Arias, Bárbara 17 Aubry, Jean-Michel 18 Hasler, Roland 19 Richard-Lepouriel, Hélène 20 Perroud, Nader 21 Backlund, Lena 22 Bhattacharjee, Abesh Kumar 23 Bellivier, Frank 24 Benabarre, Antonio 25 Bengesser, Susanne 26 0000-0001-9350-4440 Biernacka, Joanna M 27 Birner, Armin 28 0000-0002-2282-134X Marie-Claire, Cynthia 29 Cervantes, Pablo 30 0000-0003-3191-0093 Chen, Hsi-Chung 31 Chillotti, Caterina 32 0000-0002-9475-086X Cichon, Sven 33 0000-0002-7799-5531 Cruceanu, Cristiana 34 0000-0003-0745-5916 Czerski, Piotr M 35 Dalkner, Nina 36 0000-0001-9491-5938 Del Zompo, Maria 37 0000-0001-9221-9226 DePaulo, J Raymond 38 0000-0002-5377-1488 Étain, Bruno 39 0000-0002-4321-4100 Jamain, Stephane 40 Falkai, Peter 41 0000-0002-1876-6368 Forstner, Andreas J 42 Frisen, Louise 43 0000-0001-6997-4215 Frye, Mark A 44 Gard, Sébastien 45 0000-0002-7987-4995 Garnham, Julie S 46 0000-0001-6262-8264 Goes, Fernando S 47 0000-0002-1304-6687 Grigoroiu-Serbanescu, Maria 48 P:(DE-2719)2811701 Fallgatter, Andreas 49 dzne Stegmaier, Sophia 50 Ethofer, Thomas 51 Biere, Silvia 52 Petrova, Kristiyana 53 Schuster, Ceylan 54 Adorjan, Kristina 55 Budde, Monika 56 Heilbronner, Maria 57 0000-0003-0930-4214 Kalman, Janos L 58 0000-0002-1357-2636 Kohshour, Mojtaba Oraki 59 Reich-Erkelenz, Daniela 60 Schaupp, Sabrina K 61 0000-0003-3105-5672 Schulte, Eva C 62 Senner, Fanny 63 Vogl, Thomas 64 Anghelescu, Ion-George 65 Arolt, Volker 66 Dannlowski, Udo 67 Dietrich, Detlef 68 Figge, Christian 69 Jäger, Markus 70 Lang, Fabian U 71 Juckel, Georg 72 Konrad, Carsten 73 0009-0007-5406-5319 Reimer, Jens 74 Schmauß, Max 75 Schmitt, Andrea 76 Spitzer, Carsten 77 von Hagen, Martin 78 P:(DE-2719)2811317 Wiltfang, Jens 79 Zimmermann, Jörg 80 0000-0002-2917-5889 Andlauer, Till F M 81 P:(DE-2719)2000047 Fischer, Andre 82 dzne Bermpohl, Felix 83 0000-0003-4286-5830 Ritter, Philipp 84 Matura, Silke 85 Gryaznova, Anna 86 Falkenberg, Irina 87 0000-0002-8386-6189 Yildiz, Cüneyt 88 Kircher, Tilo 89 0000-0002-5942-2924 Schmidt, Julia 90 0000-0002-0908-7478 Koch, Marius 91 0000-0001-8629-0579 Gade, Kathrin 92 Trost, Sarah 93 Haussleiter, Ida S 94 Lambert, Martin 95 Rohenkohl, Anja C 96 Kraft, Vivien 97 Grof, Paul 98 Hashimoto, Ryota 99 0000-0002-6621-3493 Hauser, Joanna 100 Herms, Stefan 101 Hoffmann, Per 102 Jiménez, Esther 103 Kahn, Jean-Pierre 104 Kassem, Layla 105 0000-0003-0365-3587 Kuo, Po-Hsiu 106 Kato, Tadafumi 107 Kelsoe, John 108 0000-0003-3057-6150 Kittel-Schneider, Sarah 109 Ferensztajn-Rochowiak, Ewa 110 König, Barbara 111 0000-0002-8747-5070 Kusumi, Ichiro 112 Laje, Gonzalo 113 0000-0002-4496-6451 Landén, Mikael 114 0000-0003-4987-2718 Lavebratt, Catharina 115 0000-0001-5473-3697 Leboyer, Marion 116 Leckband, Susan G 117 0000-0002-8095-2305 Tortorella, Alfonso 118 Manchia, Mirko 119 Martinsson, Lina 120 0000-0001-6219-4945 McCarthy, Michael J 121 McElroy, Susan 122 0000-0002-9516-9030 Colom, Francesc 123 0000-0003-1919-9649 Millischer, Vincent 124 Mitjans, Marina 125 Mondimore, Francis M 126 0000-0002-5287-3829 Monteleone, Palmiero 127 Nievergelt, Caroline M 128 P:(DE-2719)9000400 Nöthen, Markus M. 129 0000-0001-9156-9654 Novák, Tomas 130 O'Donovan, Claire 131 Ozaki, Norio 132 Pfennig, Andrea 133 0000-0002-9151-4319 Pisanu, Claudia 134 Potash, James B 135 P:(DE-2719)9001554 Reif, Andreas 136 0000-0001-5964-4087 Reininghaus, Eva 137 0000-0001-8403-1418 Rouleau, Guy A 138 0000-0003-0577-0381 Rybakowski, Janusz K 139 0000-0001-5011-2922 Schalling, Martin 140 0000-0003-2967-9662 Schofield, Peter R 141 Schweizer, Barbara W 142 0000-0002-6354-2662 Severino, Giovanni 143 Shilling, Paul D 144 0000-0002-9663-6243 Shimoda, Katzutaka 145 Simhandl, Christian 146 Slaney, Claire M 147 0000-0001-7415-7607 Squassina, Alessio 148 Stamm, Thomas 149 0000-0003-2712-3652 Stopkova, Pavla 150 Maj, Mario 151 0000-0003-4075-2736 Turecki, Gustavo 152 0000-0002-0548-0053 Vieta, Eduard 153 Veeh, Julia 154 0000-0002-1571-1468 Witt, Stephanie H 155 Wright, Adam 156 0000-0001-8423-2623 Zandi, Peter P 157 Mitchell, Philip B 158 Bauer, Michael 159 0000-0001-9544-3944 Alda, Martin 160 0000-0002-5236-6149 Rietschel, Marcella 161 0000-0002-9469-305X McMahon, Francis J 162 Schulze, Thomas G 163 0000-0003-1640-5611 Clark, Scott R 164 Baune, Bernhard T 165 DZNE-2024-00517 http://pub.dzne.de/record/269348/files/DZNE-2024-00517%20SUP.docx http://pub.dzne.de/record/269348/files/DZNE-2024-00517.pdf OpenAccess http://pub.dzne.de/record/269348/files/DZNE-2024-00517%20SUP.doc http://pub.dzne.de/record/269348/files/DZNE-2024-00517%20SUP.odt http://pub.dzne.de/record/269348/files/DZNE-2024-00517%20SUP.pdf http://pub.dzne.de/record/269348/files/DZNE-2024-00517.pdf?subformat=pdfa pdfa OpenAccess 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. 9FN79X2M3F NLM Chemicals Lithium 3KX376GY7L NLM Chemicals Glutamic Acid NLM Chemicals Lithium Compounds N9YNS0M02X NLM Chemicals Acetylcholine NLM Chemicals Antimanic Agents MeSH Bipolar Disorder: drug therapy MeSH Bipolar Disorder: genetics MeSH Humans MeSH Female MeSH Male MeSH Multifactorial Inheritance: genetics MeSH Adult MeSH Middle Aged MeSH Lithium: therapeutic use MeSH Lithium: pharmacology MeSH Treatment Outcome MeSH Bayes Theorem MeSH Genome-Wide Association Study: methods MeSH Glutamic Acid: metabolism MeSH Cohort Studies MeSH Lithium Compounds: therapeutic use MeSH Lithium Compounds: pharmacology MeSH Acetylcholine: metabolism MeSH Polymorphism, Single Nucleotide: genetics MeSH Antimanic Agents: therapeutic use MeSH Antimanic Agents: pharmacology StatID:(DE-HGF)0200 StatID DBCoverage SCOPUS 2023-08-25 StatID:(DE-HGF)0160 StatID DBCoverage Essential Science Indicators 2023-08-25 StatID:(DE-HGF)1050 StatID DBCoverage BIOSIS Previews 2023-08-25 StatID:(DE-HGF)1190 StatID DBCoverage Biological Abstracts 2023-08-25 StatID:(DE-HGF)0600 StatID DBCoverage Ebsco Academic Search 2023-08-25 StatID:(DE-HGF)0100 StatID JCR MOL PSYCHIATR : 2022 2023-08-25 StatID:(DE-HGF)1030 StatID DBCoverage Current Contents - Life Sciences 2023-08-25 StatID:(DE-HGF)9910 StatID IF >= 10 MOL PSYCHIATR : 2022 2023-08-25 StatID:(DE-HGF)0113 StatID WoS Science Citation Index Expanded 2023-08-25 StatID:(DE-HGF)3002 StatID DEAL Springer 2023-08-25 ger StatID:(DE-HGF)0150 StatID DBCoverage Web of Science Core Collection 2023-08-25 StatID:(DE-HGF)0510 StatID OpenAccess StatID:(DE-HGF)0030 StatID Peer Review ASC 2023-08-25 StatID:(DE-HGF)0300 StatID DBCoverage Medline 2023-08-25 LIC:(DE-HGF)CCBY4 HGFVOC Creative Commons Attribution CC BY 4.0 StatID:(DE-HGF)0199 StatID DBCoverage Clarivate Analytics Master Journal List 2023-08-25 2023 I:(DE-HGF)0 P:(DE-2719)2811701 External Institute 49 Extern I:(DE-588)1065079516 P:(DE-2719)2811317 Deutsches Zentrum für Neurodegenerative Erkrankungen 79 DZNE I:(DE-588)1065079516 P:(DE-2719)2000047 Deutsches Zentrum für Neurodegenerative Erkrankungen 82 DZNE G:(DE-HGF)POF4-353 G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-300 G:(DE-HGF)POF4 G:(DE-HGF)POF DE-HGF Gesundheit Neurodegenerative Diseases Clinical and Health Care Research 0 G:(DE-HGF)POF4-352 G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-300 G:(DE-HGF)POF4 G:(DE-HGF)POF DE-HGF Gesundheit Neurodegenerative Diseases Disease Mechanisms 1 PERI:(DE-600)1502531-7 10.1038/s41380-023-02149-1 Vol. 28, no. 12, p. 5251 - 5261 12 5251 - 5261 Molecular psychiatry 28 1359-4184 2023 610 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder. doi 10.1038/s41380-023-02149-1 pmid pmid:37433967 pmc pmc:PMC11041653 ISSN 1359-4184 ISSN 1476-5578 altmetric altmetric:151223266 London Macmillan 2023 0000-0002-7940-0335 Amare, Azmeraw T 0 English oai:pub.dzne.de:269348 openaire open_access VDB driver dnbdelivery G:(DE-HGF)POF4-353 353 - Clinical and Health Care Research (POF4-353) POF4-353 POF IV 0 G:(DE-HGF)POF4-352 352 - Disease Mechanisms (POF4-352) POF4-352 POF IV 1 I:(DE-2719)1410006 AG Wiltfang Molecular biomarkers for predictive diagnostics of neurodegenerative diseases 0 I:(DE-2719)1410002 AG Fischer Epigenetics and Systems Medicine in Neurodegenerative Diseases 1