Accès ouvert déclaré
2025
preprint
Pathway-Specific Polygenic Scores for Lithium Response for Predicting Clinical Lithium Treatment Response in Patients with Bipolar Disorder
Nigussie Tadesse Sharew, Scott R. Clark, Sergi Papiol, Urs Heilbronner, Franziska Degenhardt, Janice M. Fullerton, Liping Hou, Tatyana Shekhtman, Mazda Adli, Nirmala Akula, Kazufumi Akiyama, Raffaella Ardau, Bárbara Arias, Roland Hasler, Hélène Richard-Lepouriel, Nader Perroud, Lena Backlund, Abesh Kumar Bhattacharjee, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Joanna M. Biernacka, Armin Birner, Cynthia Marie‐Claire, Pablo Cervantes, Hsi‐Chung Chen, Caterina Chillotti, Sven Cichon, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Maria Del Zompo, J. Raymond DePaulo, Bruno Étain, Stéphane Jamain, Peter Falkai, Andreas J. Forstner, Louise Frisén, Mark A. Frye, Sébastien Gard, Julie Garnham, Fernando S. Goes, Maria Grigoroiu‐Serbânescu, Andreas J. Fallgatter, Sophia Stegmaier, Thomas Ethofer, Silvia Biere, Kristiyana Petrova, Ceylan Schuster, Kristina Adorjan, Monika Budde, Maria Heilbronner, János Kálmán, Mojtaba Oraki Kohshour, Daniela Reich‐Erkelenz, Sabrina K. Schaupp, Eva C. Schulte, Fanny Senner, Thomas Vogl, Ion‐George Anghelescu, Volker Arolt, Udo Dannlowski, Detlef E. Dietrich, Christian Figge, Markus Jäger, Fabian Lang, Georg Juckel, Carsten Konrad, Jens Reimer, Max Schmauß, Andrea Schmitt, Carsten Spitzer, Martin von Hagen, Jens Wiltfang, Jörg Zimmermann, Till F. M. Andlauer, André Fischer, Felix Bermpohl, Philipp Ritter, Silke Matura, Irina Falkenberg, Cüneyt Yildiz, Tilo Kircher, Julia Schmidt, Marius Koch, Kathrin Gade, Sarah Trost, Ida S. Haussleiter, Martin Lambert, Anja Rohenkohl, Vivien Kraft, Paul Grof, Ryota Hashimoto, Joanna Hauser, Stefan Herms, Per Hoffmann, Esther Jiménez, Jean‐Pierre Kahn, Layla Kassem, Po‐Hsiu Kuo, Tadafumi Kato, John R. Kelsoe, Sarah Kittel‐Schneider, Ewa Ferensztajn‐Rochowiak, Barbara König, Ichiro Kusumi, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G. Leckband, Alfonso Tortorella, Mirko Manchia, Lina Martinsson, Michael J. McCarthy, Susan L. McElroy, Francesc Colom, Vincent Millischer, Marina Mitjans, Francis M. Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Markus M. Nöthen, Tomáš Novák, Claire O’Donovan, Norio Ozaki, Andrea Pfennig, Claudia Pisanu, James B. Potash, Andreas Reif, Eva Z. Reininghaus, Guy A. Rouleau, Janusz Rybakowski, Martin Schalling, Peter R. Schofield, Barbara Schweizer, Giovanni Severino, Paul D. Shilling, Katzutaka Shimoda, Christian Simhandl, Claire Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopková, Mario Maj, Gustavo Turecki, Julia Veeh, Biju Viswanath, Stephanie H. Witt, A. Jordan Wright, Peter P. Zandi, Philip B. Mitchell, Michael Bauer, Martin Alda, Marcella Rietschel, Francis J. McMahon, Thomas G. Schulze, Bernhard T. Baune, Klaus Oliver Schubert, Azmeraw T. Amare
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Résumé fourni par la source
Abstract Background Polygenic scores (PGSs) hold the potential to identify patients who respond favourably to specific psychiatric treatments. However, their biological interpretations remain unclear. In this study, we developed pathway-specific PGSs (PS PGS ) for lithium response and assessed their association with clinical lithium response in patients with bipolar disorder (BD). Methods Using sets of genes involved in pathways affected by lithium, we developed nine PS PGSs and evaluated their associations with lithium response in the International Consortium on Lithium Genetics cohort (ConLi + Gen: N = 2367), validated in the combined PsyCourse (N = 105) and BipoLife (N = 102) cohorts. Lithium responsiveness was assessed using the Retrospective Assessment of the Lithium Response Phenotype Scale (ALDA scale), for categorical outcome (good vs poor response) and continuous ALDA total score. Logistic and linear regressions, adjusting for age, sex, chip type, and the first four genetic principal components, were used to test associations, after multiple testing corrections ( p <0.05). Results Response to lithium was associated with PS PGS for acetylcholine, GABA, calcium channel signalling, mitochondria, circadian rhythm, and GSK pathways, R² ranging from 0.29% to 1.91%, with R² of 3.71% for the combined PS PGS. Associations for GABA PGS and CIR PGS were replicated. In decile-based stratified analysis, patients with the highest genetic loading (10 th decile) for acetylcholine pathway genetic variants were 3.03 times (95%CI: 1.95 – 4.69) more likely to have a good lithium response than the lowest decile (1 st decile). Conclusion PS PGSs achieved predictive performance comparable with conventional genome-wide PGSs, with more biological interpretability and using a smaller list of genetic variants, facilitating further investigation into the interaction of variants and biological pathways underlying lithium response.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Pathway-Specific Polygenic Scores for Lithium Response for Predicting Clinical Lithium Treatment Response in Patients with Bipolar Disorder
- Date Crossref
- 24/03/2025
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude et ne compte pas comme une seconde source scientifique indépendante.
Institutions déclarées
Une affiliation ne permet pas de déduire la nationalité d’un auteur.
Sujets associés
Bipolar Disorder and TreatmentSchizophrenia research and treatmentGenetic Associations and Epidemiology