Molecular psychiatry · 2023

Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.

СтатьяПоддержка исследования: вне правительства СШАResearch Support, N.I.H., IntramuralПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди

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Amare Azmeraw T, Thalamuthu Anbupalam, Schubert Klaus Oliver, Fullerton Janice M, Ahmed Muktar, Hartmann Simon, Papiol Sergi, Heilbronner Urs, Degenhardt Franziska, Tekola-Ayele Fasil, Hou Liping, Hsu Yi-Hsiang, Shekhtman Tatyana, Adli Mazda, Akula Nirmala, Akiyama Kazufumi, Ardau Raffaella, Arias Bárbara, Aubry Jean-Michel, Hasler Roland, Richard-Lepouriel Hélène, Perroud Nader, Backlund Lena, Bhattacharjee Abesh Kumar, Bellivier Frank, Benabarre Antonio, Bengesser Susanne, Biernacka Joanna M, Birner Armin, Marie-Claire Cynthia, Cervantes Pablo, Chen Hsi-Chung, Chillotti Caterina, Cichon Sven, Cruceanu Cristiana, Czerski Piotr M, Dalkner Nina, Del Zompo Maria, DePaulo J Raymond, Étain Bruno, Jamain Stephane, Falkai Peter, Forstner Andreas J, Frisen Louise, Frye Mark A, Gard Sébastien, Garnham Julie S, Goes Fernando S, Grigoroiu-Serbanescu Maria, Fallgatter Andreas J, Stegmaier Sophia, Ethofer Thomas, Biere Silvia, Petrova Kristiyana, Schuster Ceylan, Adorjan Kristina, Budde Monika, Heilbronner Maria, Kalman Janos L, Kohshour Mojtaba Oraki, Reich-Erkelenz Daniela, Schaupp Sabrina K, Schulte Eva C, Senner Fanny, Vogl Thomas, Anghelescu Ion-George, Arolt Volker, Dannlowski Udo, Dietrich Detlef, Figge Christian, Jäger Markus, Lang Fabian U, Juckel Georg, Konrad Carsten, Reimer Jens, Schmauß Max, Schmitt Andrea, Spitzer Carsten, von Hagen Martin, Wiltfang Jens, Zimmermann Jörg, Andlauer Till F M, Fischer Andre, Bermpohl Felix, Ritter Philipp, Matura Silke, Gryaznova Anna, Falkenberg Irina, Yildiz Cüneyt, Kircher Tilo, Schmidt Julia, Koch Marius, Gade Kathrin, Trost Sarah, Haussleiter Ida S, Lambert Martin, Rohenkohl Anja C, Kraft Vivien, Grof Paul, Hashimoto Ryota, Hauser Joanna, Herms Stefan, Hoffmann Per, Jiménez Esther, Kahn Jean-Pierre, Kassem Layla, Kuo Po-Hsiu, 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, Tortorella Alfonso, Manchia Mirko, Martinsson Lina, McCarthy Michael J, McElroy Susan, Colom Francesc, Millischer Vincent, Mitjans Marina, Mondimore Francis M, Monteleone Palmiero, Nievergelt Caroline M, Nöthen Markus M, Novák Tomas, O'Donovan Claire, Ozaki Norio, 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, Shilling Paul D, Shimoda Katzutaka, Simhandl Christian, Slaney Claire M, Squassina Alessio, Stamm Thomas, Stopkova Pavla, Maj Mario, Turecki Gustavo, Vieta Eduard, Veeh Julia, Witt Stephanie H, Wright Adam, Zandi Peter P, Mitchell Philip B, Bauer Michael, Alda Martin, Rietschel Marcella, McMahon Francis J, Schulze Thomas G, Clark Scott R, Baune Bernhard T

Аннотация

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.

Предметные рубрики MeSH

Bipolar Disorder Humans Female Male Multifactorial Inheritance Adult Middle Aged Lithium Treatment Outcome Bayes Theorem Genome-Wide Association Study Glutamic Acid Cohort Studies Lithium Compounds Acetylcholine Polymorphism, Single Nucleotide Antimanic Agents

Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.

Ошибки и ограничения

Аннотация

Предметные рубрики MeSH