Focal adhesion is associated with lithium response in bipolar disorder: evidence from a network-based multi-omics analysis

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F24%3A43921151" target="_blank" >RIV/00023752:_____/24:43921151 - isvavai.cz</a>

Result on the web

<a href="https://www.nature.com/articles/s41380-022-01909-9" target="_blank" >https://www.nature.com/articles/s41380-022-01909-9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41380-022-01909-9" target="_blank" >10.1038/s41380-022-01909-9</a>

Result language

angličtina

Original language name

Focal adhesion is associated with lithium response in bipolar disorder: evidence from a network-based multi-omics analysis

Original language description

Lithium (Li) is one of the most effective drugs for treating bipolar disorder (BD), however, there is presently no way to predict response to guide treatment. The aim of this study is to identify functional genes and pathways that distinguish BD Li responders (LR) from BD Li non-responders (NR). An initial Pharmacogenomics of Bipolar Disorder study (PGBD) GWAS of lithium response did not provide any significant results. As a result, we then employed network-based integrative analysis of transcriptomic and genomic data. In transcriptomic study of iPSC-derived neurons, 41 significantly differentially expressed (DE) genes were identified in LR vs NR regardless of lithium exposure. In the PGBD, post-GWAS gene prioritization using the GWA-boosting (GWAB) approach identified 1119 candidate genes. Following DE-derived network propagation, there was a highly significant overlap of genes between the top 500- and top 2000-proximal gene networks and the GWAB gene list (P-hypergeometric = 1.28E-09 and 4.10E-18, respectively). Functional enrichment analyses of the top 500 proximal network genes identified focal adhesion and the extracellular matrix (ECM) as the most significant functions. Our findings suggest that the difference between LR and NR was a much greater effect than that of lithium. The direct impact of dysregulation of focal adhesion on axon guidance and neuronal circuits could underpin mechanisms of response to lithium, as well as underlying BD. It also highlights the power of integrative multi-omics analysis of transcriptomic and genomic profiling to gain molecular insights into lithium response in BD.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30215 - Psychiatry

Project

—

Continuities

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Molecular Psychiatry

ISSN

1359-4184

e-ISSN

1476-5578

Volume of the periodical

29

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

14

Pages from-to

6-19

UT code for WoS article

000982936300004

EID of the result in the Scopus database

2-s2.0-85151271786