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.

• MeSH
• Bipolar Disorder * drug therapy   genetics   MeSH
• Genome-Wide Association Study MeSH
• Focal Adhesions MeSH
• Phosphatidylinositol 3-Kinases genetics   MeSH
• Humans MeSH
• Lithium * pharmacology   therapeutic use   MeSH
• Multiomics MeSH
• Proto-Oncogene Proteins c-akt genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Phosphatidylinositol 3-Kinases MeSH
• Lithium * MeSH
• Proto-Oncogene Proteins c-akt MeSH