| Title: |
Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study |
| Authors: |
Ou, AH; Rosenthal, SB; Adli, M; Akiyama, K; Akula, N; Alda, M; Amare, AT; Ardau, R; Arias, B; Aubry, JM; Backlund, L; Bauer, M; Baune, BT; Bellivier, F; Benabarre, A; Bengesser, S; Bhattacharjee, AK; Biernacka, JM; Cervantes, P; Chen, GB; Chen, HC; Chillotti, C; Cichon, S; Clark, SR; Colom, F; Cousins, DA; Cruceanu, C; Czerski, PM; Dantas, CR; Dayer, A; Del Zompo, M; Degenhardt, F; DePaulo, JR; Étain, B; Falkai, P; Fellendorf, FT; Ferensztajn-Rochowiak, E; Forstner, AJ; Frisén, L; Frye, MA; Fullerton, JM; Gard, S; Garnham, JS; Goes, FS; Grigoroiu-Serbanescu, M; Grof, P; Gruber, O; Hashimoto, R; Hauser, J; Heilbronner, U; Herms, S; Hoffmann, P; Hofmann, A; Hou, L; Jamain, S; Jiménez, E; Kahn, JP; Kassem, L; Kato, T; Kittel-Schneider, S; König, B; Kuo, PH; Kusumi, I; Lackner, N; Laje, G; Landén, M; Lavebratt, C; Leboyer, M; Leckband, SG; Jaramillo, CAL; MacQueen, G; Maj, M; Manchia, M; Marie-Claire, C; Martinsson, L; Mattheisen, M; McCarthy, MJ; McElroy, SL; McMahon, FJ; Mitchell, PB; Mitjans, M; Mondimore, FM; Monteleone, P; Nievergelt, CM; Nöthen, MM; Novák, T; Ösby, U; Ozaki, N; Papiol, S; Perlis, RH; Pisanu, C; Potash, JB; Pfennig, A; Reich-Erkelenz, D; Reif, A; Reininghaus, EZ; Rietschel, M; Rouleau, GA; Rybakowski, JK; Schalling, M; Schofield, Peter |
| Source: |
urn:ISSN:2158-3188 ; Translational Psychiatry, 14, 1, 109 |
| Publisher Information: |
Springer Nature |
| Publication Year: |
2024 |
| Collection: |
UNSW Sydney (The University of New South Wales): UNSWorks |
| Subject Terms: |
32 Biomedical and Clinical Sciences; 3209 Neurosciences; 3202 Clinical Sciences; Brain Disorders; Genetics; Mental Health; Bipolar Disorder; Mental Illness; Human Genome; Serious Mental Illness; 4.2 Evaluation of markers and technologies; 3 Good Health and Well Being; Humans; Lithium; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Genome-Wide Association Study; Multiomics; Focal Adhesions; anzsrc-for: 32 Biomedical and Clinical Sciences; anzsrc-for: 3209 Neurosciences; anzsrc-for: 3202 Clinical Sciences; anzsrc-for: 1103 Clinical Sciences; anzsrc-for: 1117 Public Health and Health Services; anzsrc-for: 1701 Psychology; anzsrc-for: 5202 Biological psychology |
| Description: |
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 2039 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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
https://hdl.handle.net/1959.4/103893 |
| DOI: |
10.1038/s41398-024-02811-4 |
| Availability: |
https://hdl.handle.net/1959.4/103893; https://unsworks.unsw.edu.au/bitstreams/22f43485-6bdc-497d-ab79-60029459b0da/download; https://doi.org/10.1038/s41398-024-02811-4 |
| Rights: |
open access ; https://purl.org/coar/access_right/c_abf2 ; CC BY ; https://creativecommons.org/licenses/by/4.0/ ; free_to_read |
| Accession Number: |
edsbas.D65E5406 |
| Database: |
BASE |