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.
von Martin Baunacke ; Maria-Luisa Schmidt ; Christer Groeben ; Angelika Sabina Maria Borkowetz ; Christian Thomas ; Rainer Koch ; Falk Hoffmann ; Felix Chun ; Lothar Weißbach ; Johannes Huber
von Marc René Lotz ; Neelotpal Majumdar ; Vanessa Beutel ; Jana Gerlach ; Carsten Wegkamp ; Melanie Hoffmann ; Lily Kahl ; Jonas Wussow ; Henning Schlachter ; Carsten Agert ; Michael H. Breitner ; Bernd Engel ; Stefan Ewald Geißendörfer ; Lutz Hofmann ; Martin Könemund ; Michael Kurrat ; Thomas Leveringhaus ; Karsten von Maydell
NEIS Conference on Sustainable Energy Supply and Energy Storage Systems (9. : 2021 : Online) NEIS 2021 Berlin : VDE Verlag, 2021 (2021), Seite 53-60 1 Online-Ressource
von Timo Stöver ; Stefan Dazert ; Stefan K.-R. Plontke ; Sabine Maria Kramer ; Petra Ambrosch ; Christoph Arens ; Christian Stephan Betz ; Dirk Beutner ; Christopher Bohr ; Karl-Ludwig Bruchhage ; Martin Canis ; Andreas Dietz ; Orlando Guntinas-Lichius ; Rudolf Hagen ; Werner Hosemann ; Heinrich Iro ; Jens Peter Klußmann ; Andreas Knopf ; Stephan Lang ; Martin Leinung ; Thomas Lenarz ; Hubert Martin Löwenheim ; Christoph Matthias ; Robert Arndt Mlynski ; Heidi Olze ; Jonas Jae-Hyun Park ; Peter K. Plinkert ; Andreas Daniel Radeloff ; Nicole Rotter ; Claudia Rudack ; Alessandro Bozzato ; Jörg H. Schipper ; Martin Schrader ; Patrick Schuler ; Sebastian Strieth ; Boris Stuck ; Stefan Volkenstein ; Martin Westhofen ; Gregor Wolf ; Barbara Wollenberg ; Thomas Zahnert ; Johannes Zenk ; Thomas K. Hoffmann
von Ulrike Mütze ; Lucy Henze ; Florian Gleich ; Martin Lindner ; Sarah C. Grünert ; Ute Spiekerkoetter ; René Santer ; Holger Blessing ; Eva Thimm ; Regina Ensenauer ; Johannes Weigel ; Skadi Beblo ; Maria Arélin ; Julia B. Hennermann ; Thorsten Marquardt ; Iris Marquardt ; Peter Freisinger ; Johannes Krämer ; Andrea Dieckmann ; Natalie Weinhold ; Mareike Keller ; Magdalena Walter ; Katharina A. Schiergens ; Esther M. Maier ; Georg F. Hoffmann ; Sven F. Garbade ; Stefan Kölker
von Jonas Wussow ; Davood Babazadeh ; Vanessa Beutel ; Sebastian Buchholz ; Stefan Ewald Geißendörfer ; Jana Gerlach ; Neelopal Majumdar ; Karsten von Maydell ; Anand Narayan ; Melanie Hoffmann ; Lily Kahl ; Thomas Leveringhaus ; Marc Rene Lotz ; Alexandra Scheunert ; Payam Teimourzadeh Baboli ; Paul Hendrik Tiemann ; Nils Huxoll ; Oliver Werth ; Carsten Agert ; Michael H. Breitner ; Bernd Engel ; Lutz Hofmann ; Martin Könemund ; Michael Kurrat ; Sebastian Lehnhoff ; Astrid Nieße ; Hartmut Weyer
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