000280742 001__ 280742
000280742 005__ 20250907001852.0
000280742 0247_ $$2doi$$a10.1016/j.bpsgos.2025.100558
000280742 0247_ $$2pmid$$apmid:40821394
000280742 0247_ $$2pmc$$apmc:PMC12357302
000280742 0247_ $$2altmetric$$aaltmetric:179351788
000280742 037__ $$aDZNE-2025-00963
000280742 041__ $$aEnglish
000280742 082__ $$a610
000280742 1001_ $$aSharew, Nigussie T$$b0
000280742 245__ $$aPathway-Specific Polygenic Scores for Predicting Clinical Lithium Treatment Response in Patients With Bipolar Disorder.
000280742 260__ $$aAmsterdam$$bElsevier$$c2025
000280742 3367_ $$2DRIVER$$aarticle
000280742 3367_ $$2DataCite$$aOutput Types/Journal article
000280742 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1756976214_4382
000280742 3367_ $$2BibTeX$$aARTICLE
000280742 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000280742 3367_ $$00$$2EndNote$$aJournal Article
000280742 520__ $$aPolygenic scores (PGSs) hold the potential to identify patients who respond favorably to specific psychiatric treatments. However, their biological interpretation remains unclear. In this study, we developed pathway-specific PGSs (PSPGSs) for lithium response and assessed their association with clinical lithium response in patients with bipolar disorder.Using sets of genes involved in pathways affected by lithium, we developed 9 PSPGSs and evaluated their associations with lithium response in the International Consortium on Lithium Genetics (ConLi+Gen) (N = 2367), with validation in combined PsyCourse (Pathomechanisms and Signatures in the Longitudinal Course of Psychosis) (N = 105) and BipoLife (N = 102) cohorts. The association between each PSPGS and lithium response-defined both as a continuous ALDA score and a categorical outcome (good vs. poor responses)-was evaluated using regression models, with adjustment for confounders. The cutoff for a significant association was p < .05 after multiple testing correction.The PGSs for acetylcholine, GABA (gamma-aminobutyric acid), and mitochondria were associated with response to lithium in both categorical and continuous outcomes. However, the PGSs for calcium channel, circadian rhythm, and GSK (glycogen synthase kinase) were associated only with the continuous outcome. Each score explained 0.29% to 1.91% of the variance in the categorical and 0.30% to 1.54% of the variance in the continuous outcomes. A multivariate model combining PSPGSs that showed significant associations in the univariate analysis (combined PSPGS) increased the percentage of variance explained (R 2) to 3.71% and 3.18% for the categorical and continuous outcomes, respectively. Associations for PGSs for GABA and circadian rhythm were replicated. Patients with the highest genetic loading (10th decile) for acetylcholine variants were 3.03 times more likely (95% CI, 1.95 to 4.69) to show a good lithium response (categorical outcome) than patients with the lowest genetic loading (1st decile).PSPGSs achieved predictive performance comparable to the conventional genome-wide PGSs, with the added advantage of biological interpretability using a smaller list of genetic variants.
000280742 536__ $$0G:(DE-HGF)POF4-353$$a353 - Clinical and Health Care Research (POF4-353)$$cPOF4-353$$fPOF IV$$x0
000280742 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x1
000280742 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000280742 650_7 $$2Other$$aBipolar disorder
000280742 650_7 $$2Other$$aLithium
000280742 650_7 $$2Other$$aPharmacogenomics
000280742 650_7 $$2Other$$aPolygenic score
000280742 650_7 $$2Other$$aPsychiatry
000280742 7001_ $$aClark, Scott R$$b1
000280742 7001_ $$aPapiol, Sergi$$b2
000280742 7001_ $$aHeilbronner, Urs$$b3
000280742 7001_ $$aDegenhardt, Franziska$$b4
000280742 7001_ $$aFullerton, Janice M$$b5
000280742 7001_ $$aHou, Liping$$b6
000280742 7001_ $$aShekhtman, Tatyana$$b7
000280742 7001_ $$aAdli, Mazda$$b8
000280742 7001_ $$aAkula, Nirmala$$b9
000280742 7001_ $$aAkiyama, Kazufumi$$b10
000280742 7001_ $$aArdau, Raffaella$$b11
000280742 7001_ $$aArias, Bárbara$$b12
000280742 7001_ $$aHasler, Roland$$b13
000280742 7001_ $$aRichard-Lepouriel, Hélène$$b14
000280742 7001_ $$aPerroud, Nader$$b15
000280742 7001_ $$aBacklund, Lena$$b16
000280742 7001_ $$aBhattacharjee, Abesh Kumar$$b17
000280742 7001_ $$aBellivier, Frank$$b18
000280742 7001_ $$aBenabarre, Antonio$$b19
000280742 7001_ $$aBengesser, Susanne$$b20
000280742 7001_ $$aBiernacka, Joanna M$$b21
000280742 7001_ $$aBirner, Armin$$b22
000280742 7001_ $$aMarie-Claire, Cynthia$$b23
000280742 7001_ $$aCervantes, Pablo$$b24
000280742 7001_ $$aChen, Hsi-Chung$$b25
000280742 7001_ $$aChillotti, Caterina$$b26
000280742 7001_ $$aCichon, Sven$$b27
000280742 7001_ $$aCruceanu, Cristiana$$b28
000280742 7001_ $$aCzerski, Piotr M$$b29
000280742 7001_ $$aDalkner, Nina$$b30
000280742 7001_ $$aDel Zompo, Maria$$b31
000280742 7001_ $$aDePaulo, J Raymond$$b32
000280742 7001_ $$aÉtain, Bruno$$b33
000280742 7001_ $$aJamain, Stephane$$b34
000280742 7001_ $$aFalkai, Peter$$b35
000280742 7001_ $$aForstner, Andreas J$$b36
000280742 7001_ $$aFrisen, Louise$$b37
000280742 7001_ $$aFrye, Mark A$$b38
000280742 7001_ $$aGard, Sébastien$$b39
000280742 7001_ $$aGarnham, Julie S$$b40
000280742 7001_ $$aGoes, Fernando S$$b41
000280742 7001_ $$aGrigoroiu-Serbanescu, Maria$$b42
000280742 7001_ $$0P:(DE-2719)2811701$$aFallgatter, Andreas$$b43
000280742 7001_ $$aStegmaier, Sophia$$b44
000280742 7001_ $$aEthofer, Thomas$$b45
000280742 7001_ $$aBiere, Silvia$$b46
000280742 7001_ $$aPetrova, Kristiyana$$b47
000280742 7001_ $$aSchuster, Ceylan$$b48
000280742 7001_ $$aAdorjan, Kristina$$b49
000280742 7001_ $$aBudde, Monika$$b50
000280742 7001_ $$aHeilbronner, Maria$$b51
000280742 7001_ $$aKalman, Janos L$$b52
000280742 7001_ $$aKohshour, Mojtaba Oraki$$b53
000280742 7001_ $$aReich-Erkelenz, Daniela$$b54
000280742 7001_ $$aSchaupp, Sabrina K$$b55
000280742 7001_ $$aSchulte, Eva C$$b56
000280742 7001_ $$aSenner, Fanny$$b57
000280742 7001_ $$aVogl, Thomas$$b58
000280742 7001_ $$aAnghelescu, Ion-George$$b59
000280742 7001_ $$aArolt, Volker$$b60
000280742 7001_ $$aDannlowski, Udo$$b61
000280742 7001_ $$aDietrich, Detlef E$$b62
000280742 7001_ $$aFigge, Christian$$b63
000280742 7001_ $$aJäger, Markus$$b64
000280742 7001_ $$aLang, Fabian U$$b65
000280742 7001_ $$aJuckel, Georg$$b66
000280742 7001_ $$aKonrad, Carsten$$b67
000280742 7001_ $$aReimer, Jens$$b68
000280742 7001_ $$aSchmauß, Max$$b69
000280742 7001_ $$aSchmitt, Andrea$$b70
000280742 7001_ $$aSpitzer, Carsten$$b71
000280742 7001_ $$avon Hagen, Martin$$b72
000280742 7001_ $$0P:(DE-2719)2811317$$aWiltfang, Jens$$b73
000280742 7001_ $$aZimmermann, Jörg$$b74
000280742 7001_ $$0P:(DE-2719)2000047$$aFischer, Andre$$b75
000280742 7001_ $$aBermpohl, Felix$$b76
000280742 7001_ $$aRitter, Philipp$$b77
000280742 7001_ $$aMatura, Silke$$b78
000280742 7001_ $$aGryaznova, Anna$$b79
000280742 7001_ $$aFalkenberg, Irina$$b80
000280742 7001_ $$aYildiz, Cüneyt$$b81
000280742 7001_ $$aKircher, Tilo$$b82
000280742 7001_ $$aSchmidt, Julia$$b83
000280742 7001_ $$aKoch, Marius$$b84
000280742 7001_ $$aGade, Kathrin$$b85
000280742 7001_ $$aTrost, Sarah$$b86
000280742 7001_ $$aAndlauer, Till F M$$b87
000280742 7001_ $$aHaussleiter, Ida S$$b88
000280742 7001_ $$aLambert, Martin$$b89
000280742 7001_ $$aRohenkohl, Anja C$$b90
000280742 7001_ $$aKraft, Vivien$$b91
000280742 7001_ $$aGrof, Paul$$b92
000280742 7001_ $$aHashimoto, Ryota$$b93
000280742 7001_ $$aHauser, Joanna$$b94
000280742 7001_ $$aHerms, Stefan$$b95
000280742 7001_ $$aHoffmann, Per$$b96
000280742 7001_ $$aJiménez, Esther$$b97
000280742 7001_ $$aKahn, Jean-Pierre$$b98
000280742 7001_ $$aKassem, Layla$$b99
000280742 7001_ $$aKuo, Po-Hsiu$$b100
000280742 7001_ $$aKato, Tadafumi$$b101
000280742 7001_ $$aKelsoe, John$$b102
000280742 7001_ $$aKittel-Schneider, Sarah$$b103
000280742 7001_ $$aFerensztajn-Rochowiak, Ewa$$b104
000280742 7001_ $$aKönig, Barbara$$b105
000280742 7001_ $$aKusumi, Ichiro$$b106
000280742 7001_ $$aLaje, Gonzalo$$b107
000280742 7001_ $$aLandén, Mikael$$b108
000280742 7001_ $$aLavebratt, Catharina$$b109
000280742 7001_ $$aLeboyer, Marion$$b110
000280742 7001_ $$aLeckband, Susan G$$b111
000280742 7001_ $$aTortorella, Alfonso$$b112
000280742 7001_ $$aManchia, Mirko$$b113
000280742 7001_ $$aMartinsson, Lina$$b114
000280742 7001_ $$aMcCarthy, Michael J$$b115
000280742 7001_ $$aMcElroy, Susan$$b116
000280742 7001_ $$aColom, Francesc$$b117
000280742 7001_ $$aMillischer, Vincent$$b118
000280742 7001_ $$aMitjans, Marina$$b119
000280742 7001_ $$aMondimore, Francis M$$b120
000280742 7001_ $$aMonteleone, Palmiero$$b121
000280742 7001_ $$aNievergelt, Caroline M$$b122
000280742 7001_ $$aNöthen, Markus M$$b123
000280742 7001_ $$aNovák, Tomas$$b124
000280742 7001_ $$aO'Donovan, Claire$$b125
000280742 7001_ $$aOzaki, Norio$$b126
000280742 7001_ $$aPfennig, Andrea$$b127
000280742 7001_ $$aPisanu, Claudia$$b128
000280742 7001_ $$aPotash, James B$$b129
000280742 7001_ $$aReif, Andreas$$b130
000280742 7001_ $$aReininghaus, Eva$$b131
000280742 7001_ $$aRouleau, Guy A$$b132
000280742 7001_ $$aRybakowski, Janusz K$$b133
000280742 7001_ $$aSchalling, Martin$$b134
000280742 7001_ $$aSchofield, Peter R$$b135
000280742 7001_ $$aSchweizer, Barbara W$$b136
000280742 7001_ $$aSeverino, Giovanni$$b137
000280742 7001_ $$aShilling, Paul D$$b138
000280742 7001_ $$aShimoda, Katzutaka$$b139
000280742 7001_ $$aSimhandl, Christian$$b140
000280742 7001_ $$aSlaney, Claire M$$b141
000280742 7001_ $$aSquassina, Alessio$$b142
000280742 7001_ $$aStamm, Thomas$$b143
000280742 7001_ $$aStopkova, Pavla$$b144
000280742 7001_ $$aMaj, Mario$$b145
000280742 7001_ $$aTurecki, Gustavo$$b146
000280742 7001_ $$aVieta, Eduard$$b147
000280742 7001_ $$aVeeh, Julia$$b148
000280742 7001_ $$aViswanath, Biju$$b149
000280742 7001_ $$aWitt, Stephanie H$$b150
000280742 7001_ $$aWright, Adam$$b151
000280742 7001_ $$aZandi, Peter P$$b152
000280742 7001_ $$aMitchell, Philip B$$b153
000280742 7001_ $$aBauer, Michael$$b154
000280742 7001_ $$aAlda, Martin$$b155
000280742 7001_ $$aRietschel, Marcella$$b156
000280742 7001_ $$aMcMahon, Francis J$$b157
000280742 7001_ $$aSchulze, Thomas G$$b158
000280742 7001_ $$aBaune, Bernhard T$$b159
000280742 7001_ $$aSchubert, Klaus Oliver$$b160
000280742 7001_ $$aAmare, Azmeraw T$$b161
000280742 773__ $$0PERI:(DE-600)3094992-0$$a10.1016/j.bpsgos.2025.100558$$gVol. 5, no. 5, p. 100558 -$$n5$$p100558$$tBiological psychiatry: global open science$$v5$$x2667-1743$$y2025
000280742 8564_ $$uhttps://pub.dzne.de/record/280742/files/DZNE-2025-00963%20SUP.zip
000280742 8564_ $$uhttps://pub.dzne.de/record/280742/files/DZNE-2025-00963.pdf$$yOpenAccess
000280742 8564_ $$uhttps://pub.dzne.de/record/280742/files/DZNE-2025-00963.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000280742 909CO $$ooai:pub.dzne.de:280742$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire
000280742 9101_ $$0I:(DE-HGF)0$$6P:(DE-2719)2811701$$aExternal Institute$$b43$$kExtern
000280742 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2811317$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b73$$kDZNE
000280742 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2000047$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b75$$kDZNE
000280742 9131_ $$0G:(DE-HGF)POF4-353$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vClinical and Health Care Research$$x0
000280742 9131_ $$0G:(DE-HGF)POF4-352$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vDisease Mechanisms$$x1
000280742 9141_ $$y2025
000280742 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2024-12-28
000280742 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2024-12-28
000280742 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2024-12-28
000280742 915__ $$0LIC:(DE-HGF)CCBYNCND4$$2HGFVOC$$aCreative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0
000280742 915__ $$0StatID:(DE-HGF)0112$$2StatID$$aWoS$$bEmerging Sources Citation Index$$d2024-12-28
000280742 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2022-11-10T08:42:22Z
000280742 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2022-11-10T08:42:22Z
000280742 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2024-12-28
000280742 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2024-12-28
000280742 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000280742 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Anonymous peer review$$d2022-11-10T08:42:22Z
000280742 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2024-12-28
000280742 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2024-12-28
000280742 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2024-12-28
000280742 9201_ $$0I:(DE-2719)1410006$$kAG Wiltfang$$lMolecular biomarkers for predictive diagnostics of neurodegenerative diseases$$x0
000280742 9201_ $$0I:(DE-2719)1410002$$kAG Fischer$$lEpigenetics and Systems Medicine in Neurodegenerative Diseases$$x1
000280742 980__ $$ajournal
000280742 980__ $$aVDB
000280742 980__ $$aUNRESTRICTED
000280742 980__ $$aI:(DE-2719)1410006
000280742 980__ $$aI:(DE-2719)1410002
000280742 9801_ $$aFullTexts