학술논문
Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder.
Document Type
Author
Amare, Azmeraw; Thalamuthu, Anbupalam; Schubert, Klaus Oliver; Fullerton, Janice; Ahmed, Muktar; Hartmann, Simon; Papiol, Sergi; Heilbronner, Urs; Degenhardt, Franziska; Tekola-Ayele, Fasil; Hou, Liping; Hsu, Yi-Hsiang; Shekhtman, Tatyana; Adli, Mazda; Akula, Nirmala; Akiyama, Kazufumi; Ardau, Raffaella; Arias, Bárbara; Aubry, Jean-Michel; Backlund, Lena; Bhattacharjee, Abesh Kumar; Bellivier, Frank; Benabarre, Antoni; Bengesser, Susanne; Biernacka, Joanna; Birner, Armin; Marie-Claire, Cynthia; Cervantes, Pablo; Chen, Hsi-Chung; Chillotti, Caterina; Cichon, Sven; Cruceanu, Cristiana; Czerski, Piotr; Dalkner, Nina; Zompo, Maria Del; DePaulo, J Raymond; Etain, Bruno; Jamain, Stéphane; Falkai, Peter; Forstner, Andreas J; Frisén, Louise; Frye, Mark; Gard, Sébastien; Garnham, Julie; Goes, Fernando; Grigoroiu-Serbanescu, Maria; Fallgatter, Andreas; Stegmaier, Sophia; Ethofer, Thomas; Biere, Silvia; Petrova, Kristiyana; Schuster, Ceylan; Adorjan, Kristina; Budde, Monika; Heilbronner, Maria; Kalman, Janos; Kohshour, Mojtaba Oraki; Reich-Erkelenz, Daniela; Schaupp, Sabrina; Schulte, Eva; Senner, Fanny; Vogl, Thomas; Anghelescu, Ion-George; Arolt, Volker; Dannlowski, Udo; Dietrich, Detlef E; Figge, Christian; Jäger, Markus; Lang, Fabian; Juckel, Georg; Spitzer, Carsten; Reimer, Jens; Schmauß, Max; Schmitt, Andrea; Konrad, Carsten; von Hagen, Martin; Wiltfang, Jens; Zimmermann, Jörg; Andlauer, Till; Fischer, Andre; Bermpohl, Felix; Kraft, Vivien; Matura, Silke; Gryaznova, Anna; Falkenberg, Irina; Yildiz, Cüneyt; Kircher, Tilo; Schmidt, Julia; Koch, Marius; Gade, Katrin; Trost, Sarah; Haußleiter, Ida; Lambert, Martin; Rohenkohl, Anja C; Grof, Paul; Hashimoto, Ryota; Hauser, Joanna; Herms, Stefan; Hoffmann, Per; Jiménez, Esther; Kahn, Jean-Pierre; Kassem, Layla; Kuo, Po-Hsiu; Kato, Tadafumi; Kelsoe, John; Kittel-Schneider, Sarah; Ferensztajn-Rochowiak, Ewa; König, Barbara; Kusumi, Ichiro; Laje, Gonzalo; Landén, Mikael, 1966; Lavebratt, Catharina; Leboyer, Marion; Leckband, Susan G; Tortorella, Alfonso; Manchia, Mirko; Martinsson, Lina; McCarthy, Michael; McElroy, Susan L; Colom, Francesc; Mitjans, Marina; Mondimore, Francis; Monteleone, Palmiero; Nievergelt, Caroline; Nöthen, Markus; Novak, Tomas; O'Donovan, Claire; Ozaki, Norio; Pfennig, Andrea; Pisanu, Claudia; Potash, James; Reif, Andreas; Reininghaus, Eva; Rouleau, Guy; Rybakowski, Janusz K; Schalling, Martin; Schofield, Peter; Schweizer, Barbara W; Severino, Giovanni; Shilling, Paul D; Shimoda, Kazutaka; Simhandl, Christian; Slaney, Claire; Squassina, Alessio; Stamm, Thomas; Stopkova, Pavla; Maj, Mario; Turecki, Gustavo; Vieta, Eduard; Veeh, Julia; Witt, Stephanie; Wright, Adam; Zandi, Peter; Mitchell, Philip; Bauer, Michael; Alda, Martin; Rietschel, Marcella; McMahon, Francis; Schulze, Thomas G; Millischer, Vincent; Clark, Scott; Baune, Bernhard
Source
Research square.
Subject
Language
English
Abstract
Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental 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=2,367) 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<����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������.