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| Home > Publications Database > Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder. > print |
| 001 | 269348 | ||
| 005 | 20260212164259.0 | ||
| 024 | 7 | _ | |2 doi |a 10.1038/s41380-023-02149-1 |
| 024 | 7 | _ | |2 pmid |a pmid:37433967 |
| 024 | 7 | _ | |2 pmc |a pmc:PMC11041653 |
| 024 | 7 | _ | |2 ISSN |a 1359-4184 |
| 024 | 7 | _ | |2 ISSN |a 1476-5578 |
| 024 | 7 | _ | |2 altmetric |a altmetric:151223266 |
| 037 | _ | _ | |a DZNE-2024-00517 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |0 0000-0002-7940-0335 |a Amare, Azmeraw T |b 0 |
| 245 | _ | _ | |a Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder. |
| 260 | _ | _ | |a London |b Macmillan |c 2023 |
| 336 | 7 | _ | |2 DRIVER |a article |
| 336 | 7 | _ | |2 DataCite |a Output Types/Journal article |
| 336 | 7 | _ | |0 PUB:(DE-HGF)16 |2 PUB:(DE-HGF) |a Journal Article |b journal |m journal |s 1715674675_2123 |
| 336 | 7 | _ | |2 BibTeX |a ARTICLE |
| 336 | 7 | _ | |2 ORCID |a JOURNAL_ARTICLE |
| 336 | 7 | _ | |0 0 |2 EndNote |a Journal Article |
| 520 | _ | _ | |a 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'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 < 0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P = 9.8 × 10-12, R2 = 1.9%) and continuous (P = 6.4 × 10-9, R2 = 2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th 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 × 10-4, R2 = 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. |
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| 650 | _ | 7 | |0 9FN79X2M3F |2 NLM Chemicals |a Lithium |
| 650 | _ | 7 | |0 3KX376GY7L |2 NLM Chemicals |a Glutamic Acid |
| 650 | _ | 7 | |2 NLM Chemicals |a Lithium Compounds |
| 650 | _ | 7 | |0 N9YNS0M02X |2 NLM Chemicals |a Acetylcholine |
| 650 | _ | 7 | |2 NLM Chemicals |a Antimanic Agents |
| 650 | _ | 2 | |2 MeSH |a Bipolar Disorder: drug therapy |
| 650 | _ | 2 | |2 MeSH |a Bipolar Disorder: genetics |
| 650 | _ | 2 | |2 MeSH |a Humans |
| 650 | _ | 2 | |2 MeSH |a Female |
| 650 | _ | 2 | |2 MeSH |a Male |
| 650 | _ | 2 | |2 MeSH |a Multifactorial Inheritance: genetics |
| 650 | _ | 2 | |2 MeSH |a Adult |
| 650 | _ | 2 | |2 MeSH |a Middle Aged |
| 650 | _ | 2 | |2 MeSH |a Lithium: therapeutic use |
| 650 | _ | 2 | |2 MeSH |a Lithium: pharmacology |
| 650 | _ | 2 | |2 MeSH |a Treatment Outcome |
| 650 | _ | 2 | |2 MeSH |a Bayes Theorem |
| 650 | _ | 2 | |2 MeSH |a Genome-Wide Association Study: methods |
| 650 | _ | 2 | |2 MeSH |a Glutamic Acid: metabolism |
| 650 | _ | 2 | |2 MeSH |a Cohort Studies |
| 650 | _ | 2 | |2 MeSH |a Lithium Compounds: therapeutic use |
| 650 | _ | 2 | |2 MeSH |a Lithium Compounds: pharmacology |
| 650 | _ | 2 | |2 MeSH |a Acetylcholine: metabolism |
| 650 | _ | 2 | |2 MeSH |a Polymorphism, Single Nucleotide: genetics |
| 650 | _ | 2 | |2 MeSH |a Antimanic Agents: therapeutic use |
| 650 | _ | 2 | |2 MeSH |a Antimanic Agents: pharmacology |
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| 773 | _ | _ | |0 PERI:(DE-600)1502531-7 |a 10.1038/s41380-023-02149-1 |g Vol. 28, no. 12, p. 5251 - 5261 |n 12 |p 5251 - 5261 |t Molecular psychiatry |v 28 |x 1359-4184 |y 2023 |
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