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2021-11-29

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cc-by-nc-nd (c) Schubert, Klaus Oliver et al., 2021
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/184068

Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients

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Recurs relacionat

https://doi.org/10.1038/s41398-021-01702-2

Resum

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.

Matèries

Esquizofrènia, Trastorn bipolar, Liti, Depressió psíquica

Matèries (anglès)

Schizophrenia, Manic-depressive illness, Lithium, Mental depression

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Col·leccions

Articles publicats en revistes (Medicina)
Articles publicats en revistes (Genètica, Microbiologia i Estadística)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Institut de Neurociències (UBNeuro))

Citació

SCHUBERT, Klaus oliver, THALAMUTHU, Anbupalam, AMARE, Azmeraw t., FRANK, Josef, STREIT, Fabian, ADL, Mazda, AKULA, Nirmala, AKIYAMA, Kazufumi, ARDAU, Raffaella, ARIAS SAMPÉRIZ, 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, CHEN, Hsi-chung, CHILLOTTI, Caterina, CICHON, Sven, CLARK, Scott r., CRUCEANU, Cristiana, CZERSKI, Piotr m., DALKNER, Nina, DAYER, Alexandre, DEGENHARDT, Franziska, ZOMPO, Maria del, DEPAULO, J. raymond, ÉTAIN, Bruno, FALKAI, Peter, FORSTNER, Andreas j., FRISEN, Louise, FRYE, Mark a., JIMÉNEZ MARTÍNEZ, Esther, MITJANS NIUBÓ, Marina, VIETA I PASCUAL, Eduard. Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients. _Translational Psychiatry_. 2021. Vol. 11, núm. 606. [consulta: 11 de abril de 2026]. ISSN: 2158-3188. [Disponible a: https://hdl.handle.net/2445/184068]

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