Kelsoe John, Ou Anna, Rosenthal Sara, Adli Mazda, Akiyama Kazufumi, Akula Nirmala, Alda Martin, Amare Azmeraw T, Ardau Raffaella, Arias Bárbara, Aubry Jean-Michel, Backlund Lena, Banzato Claudio, Bauer Michael, Baune Bernhard, Bellivier Frank, Benabarre Antonio, Bengesser Susanne, Abesh Bhattacharjee, Biernacka Joanna, Bui Elise, Cervantes Pablo, Chen Guo-Bo, Chen Hsi-Chung, Chillotti Caterina, Cichon Sven, Clark Scott, Colom Francesc, Cousins David, Cruceanu Cristiana, Czerski Piotr, Dantas Clarissa, Dayer Alexandre, Degenhardt Franziska, DePaulo J Raymond, Etain Bruno, Falkai Peter, Fellendorf Frederike, Ferensztajn-Rochowiak Ewa, Forstner Andreas J, Frisen Louise, Frye Mark, Fullerton Janice, Gard Sebastien, Garnham Julie, Goes Fernando, Grigoroiu-Serbanescu Maria, Grof Paul, Gruber Oliver, Hashimoto Ryota, Hauser Joanna, Heilbronner Urs, Herms Stefan, Hoffmann Per, Hofmann Andrea, Hou Liping, Jamain Stéphane, Jiménez Esther, Kahn Jean-Pierre, Kassem Layla, Kato Tadafumi, Kittel-Schneider Sarah, König Barbara, Kuo Po-Hsiu, Kusumi Ichiro, Dalkner Nina, Laje Gonzalo, Landén Mikael, Lavebratt Catharina, Leboyer Marion, Leckband Susan, Jaramillo Carlos López, MacQueen Glenda, Maj Mario, Manchia Mirko, Marie-Claire Cynthia, Martinsson Lina, Mattheisen Manuel, McCarthy Michael, McElroy Susan, McMahon Francis, Mitchell Philip, Mitjans Marina, Mondimore Francis, Monteleone Palmiero, Nievergelt Caroline, Nöthen Markus, Novak Tomas, Osby Urban, Ozaki Norio, Papiol Sergi, Perlis Roy, Pfennig Andrea, Potash James, Reich-Erkelenz Daniela, Reif Andreas, Reininghaus Eva, Rietschel Marcella, Rouleau Guy, Rybakowski Janusz K, Schalling Martin, Schofield Peter, Schubert Klaus Oliver, Schulze Thomas, Schweizer Barbara, Seemüller Florian, Severino Giovanni, Shekhtman Tatyana, Shilling Paul, Shimoda Kazutaka, Simhandl Christian, Slaney Claire, Squassina Alessio, Stamm Thomas, Stopkova Pavla, Tighe Sarah, Tortorella Alfonso, Turecki Gustavo, Vieta Eduard, Volkert Julia, Witt Stephanie, Wray Naomi, Wright Adam, Young Trevor, Zandi Peter, Zompo Maria Del
University of California San Diego.
Department of Biological Psychiatry and Neuroscience, Dokkyo Medical University.
Res Sq. 2023 Oct 3:rs.3.rs-3258813. doi: 10.21203/rs.3.rs-3258813/v1.
Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2,039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.
锂盐是双相情感障碍（BD）的金标准治疗药物。然而，其作用机制尚未完全明确，治疗效果的预测也较为有限。在我们之前结合转录组学和基因组数据的双相情感障碍药物基因组学（PGBD）样本的多组学研究中，我们发现粘着斑、细胞外基质（ECM）和PI3K-Akt信号网络与锂盐反应相关。在本研究中，我们在一项针对国际锂盐遗传学联盟（ConLiGen）研究中2039例独立患者样本的全基因组关联研究中，使用网络传播方法重复了我们之前研究的结果。我们确定了粘着斑和PI3K-Akt通路中的功能富集，但未发现与ECM通路有关联。我们的结果表明，神经元生长锥和PI3K-Akt信号的缺陷而非ECM蛋白的缺陷，可能影响BD患者对锂盐的反应。
