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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},
}