https://scholars.lib.ntu.edu.tw/handle/123456789/626894
標題: | Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients | 作者: | Schubert, Klaus Oliver Thalamuthu, Anbupalam Amare, Azmeraw T Frank, Joseph Streit, Fabian Adl, Mazda Akula, Nirmala Akiyama, Kazufumi Ardau, Raffaella Arias, Bárbara Aubry, Jean-Michel Backlund, Lena Bhattacharjee, Abesh Kumar Bellivier, Frank Benabarre, Antonio Bengesser, Susanne Biernacka, Joanna M Birner, Armin Marie-Claire, Cynthia Cearns, Micah Cervantes, Pablo HSI-CHUNG CHEN Chillotti, Caterina Cichon, Sven Clark, Scott R Cruceanu, Cristiana Czerski, Piotr M Dalkner, Nina Dayer, Alexandre Degenhardt, Franziska Del Zompo, Maria DePaulo, J Raymond Étain, Bruno Falkai, Peter Forstner, Andreas J Frisen, Louise Frye, Mark A Fullerton, Janice M Gard, Sébastien Garnham, Julie S Goes, Fernando S Grigoroiu-Serbanescu, Maria Grof, Paul Hashimoto, Ryota Hauser, Joanna Heilbronner, Urs Herms, Stefan Hoffmann, Per Hou, Liping Hsu, Yi-Hsiang Jamain, Stephane Jiménez, Esther Kahn, Jean-Pierre Kassem, Layla PO-HSIU KUO Kato, Tadafumi Kelsoe, John Kittel-Schneider, Sarah Ferensztajn-Rochowiak, Ewa König, Barbara Kusumi, Ichiro Laje, Gonzalo Landén, Mikael Lavebratt, Catharina Leboyer, Marion Leckband, Susan G Maj, Mario Manchia, Mirko Martinsson, Lina McCarthy, Michael J McElroy, Susan Colom, Francesc Mitjans, Marina Mondimore, Francis M Monteleone, Palmiero Nievergelt, Caroline M Nöthen, Markus M Novák, Tomas O'Donovan, Claire Ozaki, Norio Ösby, Urban Papiol, Sergi Pfennig, Andrea Pisanu, Claudia Potash, James B Reif, Andreas Reininghaus, Eva Rouleau, Guy A Rybakowski, Janusz K Schalling, Martin Schofield, Peter R Schweizer, Barbara W Severino, Giovanni Shekhtman, Tatyana Shilling, Paul D Shimoda, Katzutaka Simhandl, Christian Slaney, Claire M Squassina, Alessio Stamm, Thomas Stopkova, Pavla Tekola-Ayele, Fasil Tortorella, Alfonso Turecki, Gustavo Veeh, Julia Vieta, Eduard Witt, Stephanie H Roberts, Gloria Zandi, Peter P Alda, Martin Bauer, Michael McMahon, Francis J Mitchell, Philip B Schulze, Thomas G Rietschel, Marcella Baune, Bernhard T |
關鍵字: | GENOME-WIDE ASSOCIATION; COMPARATIVE EFFICACY; METAANALYSIS; DISEASE; MANIA | 公開日期: | 29-十一月-2021 | 出版社: | SPRINGERNATURE | 卷: | 11 | 期: | 1 | 來源出版物: | Translational psychiatry | 摘要: | Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium's therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes. We used fixed effect meta-analysis techniques to develop meta-analytic polygenic risk scores (MET-PRS) from combinations of highly correlated psychiatric traits, namely schizophrenia (SCZ), major depression (MD) and bipolar disorder (BD). We compared the effects of cross-disorder MET-PRS and single genetic trait PRS on lithium response. For the PRS analyses, we included clinical data on lithium treatment response and genetic information for n = 2283 BD cases from the International Consortium on Lithium Genetics (ConLi+Gen; www.ConLiGen.org ). Higher SCZ and MD PRSs were associated with poorer lithium treatment response whereas BD-PRS had no association with treatment outcome. The combined MET2-PRS comprising of SCZ and MD variants (MET2-PRS) and a model using SCZ and MD-PRS sequentially improved response prediction, compared to single-disorder PRS or to a combined score using all three traits (MET3-PRS). Patients in the highest decile for MET2-PRS loading had 2.5 times higher odds of being classified as poor responders than patients with the lowest decile MET2-PRS scores. An exploratory functional pathway analysis of top MET2-PRS variants was conducted. Findings may inform the development of future testing strategies for personalized lithium prescribing in BD. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/626894 | ISSN: | 2158-3188 | DOI: | 10.1038/s41398-021-01702-2 |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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