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Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder.

Azmeraw T AmareAnbupalam ThalamuthuKlaus Oliver SchubertJanice M FullertonMuktar AhmedSimon HartmannSergi PapiolUrs HeilbronnerFranziska DegenhardtFasil Tekola-AyeleLiping HouYi-Hsiang HsuTatyana ShekhtmanMazda AdliNirmala AkulaKazufumi AkiyamaRaffaella ArdauBárbara AriasJean-Michel AubryLena BacklundAbesh Kumar BhattacharjeeFrank BellivierAntoni BenabarreSusanne BengesserJoanna M BiernackaArmin BirnerCynthia Marie-ClairePablo CervantesHsi-Chung ChenCaterina ChillottiSven CichonCristiana CruceanuPiotr M CzerskiNina DalknerMaria Del ZompoJ Raymond DePauloBruno EtainStéphane JamainPeter FalkaiAndreas J ForstnerLouise FrisénMark A FryeSébastien GardJulie S GarnhamFernando S GoesMaria Grigoroiu-SerbanescuAndreas FallgatterSophia StegmaierThomas EthoferSilvia BiereKristiyana PetrovaCeylan SchusterKristina AdorjanMonika BuddeMaria HeilbronnerJanos L KalmanMojtaba Oraki KohshourDaniela Reich-ErkelenzSabrina SchauppEva C SchulteFanny SennerThomas VoglIon-George AnghelescuVolker AroltUdo DannlowskiDetlef E DietrichChristian FiggeMarkus JägerFabian LangGeorg JuckelCarsten SpitzerJens ReimerMax SchmaußAndrea SchmittCarsten KonradMartin von HagenJens WiltfangJörg ZimmermannTill F M AndlauerAndre FischerFelix BermpohlVivien KraftSilke MaturaAnna GryaznovaIrina FalkenbergCüneyt YildizTilo KircherJulia SchmidtMarius KochKatrin GadeSarah TrostIda HaußleiterMartin LambertAnja C RohenkohlVivien KraftPaul GrofRyota HashimotoJoanna HauserStefan HermsPer HoffmannEsther JiménezJean-Pierre KahnLayla KassemPo-Hsiu KuoTadafumi KatoJohn KelsoeKatharina LichterEwa Ferensztajn-RochowiakBarbara KönigIchiro KusumiGonzalo LajeMikaél LandénCatharina LavebrattMarion LeboyerSusan G LeckbandAlfonso TortorellaMirko ManchiaLina MartinssonMichael J McCarthySusan L McElroyFrancesc ColomMarina MitjansFrancis MondimorePalmiero MonteleoneCaroline NievergeltMarkus Maria NöthenTomáš NovákClaire O'DonovanNorio OzakiAndrea PfennigClaudia PisanuJames PotashAndreas ReifEva Z ReininghausGuy A RouleauJanusz K RybakowskiMartin SchallingPeter R SchofieldBarbara W SchweizerGiovanni SeverinoPaul D ShillingKatzutaka ShimodaChristian SimhandlClaire SlaneyAlessio SquassinaThomas StammPavla StopkovaMario MajGustavo TureckiEduard VietaJulia VeehStephanie-H WittAdam WrightPeter P ZandiPhilip MitchellMichael BauerMartin AldaMarcella D C RietschelFrancis J McMahonThomas G SchulzeVincent MillischerScott Richard ClarkBernhard Baune
Published in: Research square (2023)
Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental 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=2,367) 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<����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������.
Keyphrases
  • bipolar disorder
  • solid state
  • genome wide
  • newly diagnosed
  • ejection fraction
  • major depressive disorder
  • prognostic factors
  • dna methylation
  • mental health
  • copy number
  • gene expression