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@ARTICLE{Amare:269348,
      author       = {Amare, Azmeraw T and Thalamuthu, Anbupalam and Schubert,
                      Klaus Oliver and Fullerton, Janice M and Ahmed, Muktar and
                      Hartmann, Simon and Papiol, Sergi and Heilbronner, Urs and
                      Degenhardt, Franziska and Tekola-Ayele, Fasil and Hou,
                      Liping and Hsu, Yi-Hsiang and Shekhtman, Tatyana and Adli,
                      Mazda and Akula, Nirmala and Akiyama, Kazufumi and Ardau,
                      Raffaella and Arias, Bárbara and Aubry, Jean-Michel and
                      Hasler, Roland and Richard-Lepouriel, Hélène and Perroud,
                      Nader and Backlund, Lena and Bhattacharjee, Abesh Kumar and
                      Bellivier, Frank and Benabarre, Antonio and Bengesser,
                      Susanne and Biernacka, Joanna M and Birner, Armin and
                      Marie-Claire, Cynthia and Cervantes, Pablo and Chen,
                      Hsi-Chung and Chillotti, Caterina and Cichon, Sven and
                      Cruceanu, Cristiana and Czerski, Piotr M and Dalkner, Nina
                      and Del Zompo, Maria and DePaulo, J Raymond and Étain,
                      Bruno and Jamain, Stephane and Falkai, Peter and Forstner,
                      Andreas J and Frisen, Louise and Frye, Mark A and Gard,
                      Sébastien and Garnham, Julie S and Goes, Fernando S and
                      Grigoroiu-Serbanescu, Maria and Fallgatter, Andreas and
                      Stegmaier, Sophia and Ethofer, Thomas and Biere, Silvia and
                      Petrova, Kristiyana and Schuster, Ceylan and Adorjan,
                      Kristina and Budde, Monika and Heilbronner, Maria and
                      Kalman, Janos L and Kohshour, Mojtaba Oraki and
                      Reich-Erkelenz, Daniela and Schaupp, Sabrina K and Schulte,
                      Eva C and Senner, Fanny and Vogl, Thomas and Anghelescu,
                      Ion-George and Arolt, Volker and Dannlowski, Udo and
                      Dietrich, Detlef and Figge, Christian and Jäger, Markus and
                      Lang, Fabian U and Juckel, Georg and Konrad, Carsten and
                      Reimer, Jens and Schmauß, Max and Schmitt, Andrea and
                      Spitzer, Carsten and von Hagen, Martin and Wiltfang, Jens
                      and Zimmermann, Jörg and Andlauer, Till F M and Fischer,
                      Andre and Bermpohl, Felix and Ritter, Philipp and Matura,
                      Silke and Gryaznova, Anna and Falkenberg, Irina and Yildiz,
                      Cüneyt and Kircher, Tilo and Schmidt, Julia and Koch,
                      Marius and Gade, Kathrin and Trost, Sarah and Haussleiter,
                      Ida S and Lambert, Martin and Rohenkohl, Anja C and Kraft,
                      Vivien and Grof, Paul and Hashimoto, Ryota and Hauser,
                      Joanna and Herms, Stefan and Hoffmann, Per and Jiménez,
                      Esther and Kahn, Jean-Pierre and Kassem, Layla and Kuo,
                      Po-Hsiu and Kato, Tadafumi and Kelsoe, John and
                      Kittel-Schneider, Sarah and Ferensztajn-Rochowiak, Ewa and
                      König, Barbara and Kusumi, Ichiro and Laje, Gonzalo and
                      Landén, Mikael and Lavebratt, Catharina and Leboyer, Marion
                      and Leckband, Susan G and Tortorella, Alfonso and Manchia,
                      Mirko and Martinsson, Lina and McCarthy, Michael J and
                      McElroy, Susan and Colom, Francesc and Millischer, Vincent
                      and Mitjans, Marina and Mondimore, Francis M and Monteleone,
                      Palmiero and Nievergelt, Caroline M and Nöthen, Markus M.
                      and Novák, Tomas and O'Donovan, Claire and Ozaki, Norio and
                      Pfennig, Andrea and Pisanu, Claudia and Potash, James B and
                      Reif, Andreas and Reininghaus, Eva and Rouleau, Guy A and
                      Rybakowski, Janusz K and Schalling, Martin and Schofield,
                      Peter R and Schweizer, Barbara W and Severino, Giovanni and
                      Shilling, Paul D and Shimoda, Katzutaka and Simhandl,
                      Christian and Slaney, Claire M and Squassina, Alessio and
                      Stamm, Thomas and Stopkova, Pavla and Maj, Mario and
                      Turecki, Gustavo and Vieta, Eduard and Veeh, Julia and Witt,
                      Stephanie H and Wright, Adam and Zandi, Peter P and
                      Mitchell, Philip B and Bauer, Michael and Alda, Martin and
                      Rietschel, Marcella and McMahon, Francis J and Schulze,
                      Thomas G and Clark, Scott R and Baune, Bernhard T},
      title        = {{A}ssociation of polygenic score and the involvement of
                      cholinergic and glutamatergic pathways with lithium
                      treatment response in patients with bipolar disorder.},
      journal      = {Molecular psychiatry},
      volume       = {28},
      number       = {12},
      issn         = {1359-4184},
      address      = {London},
      publisher    = {Macmillan},
      reportid     = {DZNE-2024-00517},
      pages        = {5251 - 5261},
      year         = {2023},
      abstract     = {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.},
      keywords     = {Bipolar Disorder: drug therapy / Bipolar Disorder: genetics
                      / Humans / Female / Male / Multifactorial Inheritance:
                      genetics / Adult / Middle Aged / Lithium: therapeutic use /
                      Lithium: pharmacology / Treatment Outcome / Bayes Theorem /
                      Genome-Wide Association Study: methods / Glutamic Acid:
                      metabolism / Cohort Studies / Lithium Compounds: therapeutic
                      use / Lithium Compounds: pharmacology / Acetylcholine:
                      metabolism / Polymorphism, Single Nucleotide: genetics /
                      Antimanic Agents: therapeutic use / Antimanic Agents:
                      pharmacology / Lithium (NLM Chemicals) / Glutamic Acid (NLM
                      Chemicals) / Lithium Compounds (NLM Chemicals) /
                      Acetylcholine (NLM Chemicals) / Antimanic Agents (NLM
                      Chemicals)},
      cin          = {AG Wiltfang / AG Fischer},
      ddc          = {610},
      cid          = {I:(DE-2719)1410006 / I:(DE-2719)1410002},
      pnm          = {353 - Clinical and Health Care Research (POF4-353) / 352 -
                      Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37433967},
      pmc          = {pmc:PMC11041653},
      doi          = {10.1038/s41380-023-02149-1},
      url          = {https://pub.dzne.de/record/269348},
}