Sökning: onr:"swepub:oai:gup.ub.gu.se/332981" > Association of poly...
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000 | 10385naa a2202305 4500 | |
001 | oai:gup.ub.gu.se/332981 | |
003 | SwePub | |
008 | 240910s2023 | |||||||||||000 ||eng| | |
009 | oai:prod.swepub.kib.ki.se:153440760 | |
024 | 7 | a https://gup.ub.gu.se/publication/3329812 URI |
024 | 7 | a https://doi.org/10.1038/s41380-023-02149-12 DOI |
024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1534407602 URI |
040 | a (SwePub)gud (SwePub)ki | |
041 | a eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Amare, Azmeraw T4 aut |
245 | 1 0 | a Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder. |
264 | 1 | c 2023 |
520 | a Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder 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. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Psykiatri0 (SwePub)302152 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Psychiatry0 (SwePub)302152 hsv//eng |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicin0 (SwePub)3022 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicine0 (SwePub)3022 hsv//eng |
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700 | 1 | a Landén, Mikael,d 1966u Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry4 aut0 (Swepub:gu)xlandt |
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710 | 2 | a Karolinska Institutetb Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi4 org |
773 | 0 | t Molecular psychiatryg 28, s. 5251-5261q 28<5251-5261x 1476-5578 |
856 | 4 8 | u https://gup.ub.gu.se/publication/332981 |
856 | 4 8 | u https://doi.org/10.1038/s41380-023-02149-1 |
856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:153440760 |
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