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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F24%3A43921144" target="_blank" >RIV/00023752:_____/24:43921144 - isvavai.cz</a>

Result on the web

<a href="https://www.nature.com/articles/s41380-023-02149-1" target="_blank" >https://www.nature.com/articles/s41380-023-02149-1</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41380-023-02149-1" target="_blank" >10.1038/s41380-023-02149-1</a>

Result language

angličtina

Original language name

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

Original language description

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&apos;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 &lt; 0.05. Li-PGS(+) was positively associated with lithium treatment response in the ConLi(+)Gen cohort, in both the categorical (P = 9.8 x 10(-)(12), R-2 = 1.9%) and continuous (P = 6.4 x 10(-)(9), R-2 = 2.6%) outcomes. Compared to bipolar patients in the 1(st) decile of the risk distribution, individuals in the 10(th) 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 x 10(-)(4), R-2 = 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.

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

28

Issue of the periodical within the volume

12

Country of publishing house

GB - UNITED KINGDOM

Number of pages

11

Pages from-to

5251-5261

UT code for WoS article

001027796900003

EID of the result in the Scopus database

2-s2.0-85164527779