Polygenic risk scores across the extended psychosis spectrum

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorSMIGIELSKI, Lukasz
dc.contributor.authorPAPIOL, Sergi
dc.contributor.authorTHEODORIDOU, Anastasia
dc.contributor.authorHEEKEREN, Karsten
dc.contributor.authorGERSTENBERG, Miriam
dc.contributor.authorWOTRUBA, Diana
dc.contributor.authorBUECHLER, Roman
dc.contributor.authorHOFFMANN, Per
dc.contributor.authorHERMS, Stefan
dc.contributor.authorADORJAN, Kristina
dc.contributor.authorANDERSON-SCHMIDT, Heike
dc.contributor.authorBUDDE, Monika
dc.contributor.authorCOMES, Ashley L.
dc.contributor.authorGADE, Katrin
dc.contributor.authorHEILBRONNER, Maria
dc.contributor.authorHEILBRONNER, Urs
dc.contributor.authorKALMAN, Janos L.
dc.contributor.authorKLOEHN-SAGHATOLISLAM, Farahnaz
dc.contributor.authorREICH-ERKELENZ, Daniela
dc.contributor.authorSCHAUPP, Sabrina K.
dc.contributor.authorSCHULTE, Eva C.
dc.contributor.authorSENNER, Fanny
dc.contributor.authorANGHELESCU, Ion-George
dc.contributor.authorAROLT, Volker
dc.contributor.authorBAUNE, Bernhard T.
dc.contributor.authorDANNLOWSKI, Udo
dc.contributor.authorDIETRICH, Detlef E.
dc.contributor.authorFALLGATTER, Andreas J.
dc.contributor.authorFIGGE, Christian
dc.contributor.authorJAEGER, Markus
dc.contributor.authorJUCKEL, Georg
dc.contributor.authorKONRAD, Carsten
dc.contributor.authorNIERATSCHKER, Vanessa
dc.contributor.authorREIMER, Jens
dc.contributor.authorREININGHAUS, Eva
dc.contributor.authorSCHMAUSS, Max
dc.contributor.authorSPITZER, Carsten
dc.contributor.authorHAGEN, Martin von
dc.contributor.authorWILTFANG, Jens
dc.contributor.authorZIMMERMANN, Joerg
dc.contributor.authorGRYAZNOVA, Anna
dc.contributor.authorFLATAU-NAGEL, Laura
dc.contributor.authorREITT, Markus
dc.contributor.authorMEYERS, Milena
dc.contributor.authorEMONS, Barbara
dc.contributor.authorHAUSSLEITER, Ida Sybille
dc.contributor.authorLANG, Fabian U.
dc.contributor.authorBECKER, Thomas
dc.contributor.authorWIGAND, Moritz E.
dc.contributor.authorWITT, Stephanie H.
dc.contributor.authorDEGENHARDT, Franziska
dc.contributor.authorFORSTNER, Andreas J.
dc.contributor.authorRIETSCHEL, Marcella
dc.contributor.authorNOTHEN, Markus M.
dc.contributor.authorANDLAUER, Till F. M.
dc.contributor.authorROESSLER, Wulf
dc.contributor.authorWALITZA, Susanne
dc.contributor.authorFALKAI, Peter
dc.contributor.authorSCHULZE, Thomas G.
dc.contributor.authorGRUENBLATT, Edna
dc.date.accessioned2021-12-16T14:47:50Z
dc.date.available2021-12-16T14:47:50Z
dc.date.issued2021
dc.description.abstractAs early detection of symptoms in the subclinical to clinical psychosis spectrum may improve health outcomes, knowing the probabilistic susceptibility of developing a disorder could guide mitigation measures and clinical intervention. In this context, polygenic risk scores (PRSs) quantifying the additive effects of multiple common genetic variants hold the potential to predict complex diseases and index severity gradients. PRSs for schizophrenia (SZ) and bipolar disorder (BD) were computed using Bayesian regression and continuous shrinkage priors based on the latest SZ and BD genome-wide association studies (Psychiatric Genomics Consortium, third release). Eight well-phenotyped groups (n = 1580; 56% males) were assessed: control (n = 305), lower (n = 117) and higher (n = 113) schizotypy (both groups of healthy individuals), at-risk for psychosis (n = 120), BD type-I (n = 359), BD type-II (n = 96), schizoaffective disorder (n = 86), and SZ groups (n = 384). PRS differences were investigated for binary traits and the quantitative Positive and Negative Syndrome Scale. Both BD-PRS and SZ-PRS significantly differentiated controls from at-risk and clinical groups (Nagelkerke's pseudo-R-2: 1.3-7.7%), except for BD type-II for SZ-PRS. Out of 28 pairwise comparisons for SZ-PRS and BD-PRS, 9 and 12, respectively, reached the Bonferroni-corrected significance. BD-PRS differed between control and at-risk groups, but not between at-risk and BD type-I groups. There was no difference between controls and schizotypy. SZ-PRSs, but not BD-PRSs, were positively associated with transdiagnostic symptomology. Overall, PRSs support the continuum model across the psychosis spectrum at the genomic level with possible irregularities for schizotypy. The at-risk state demands heightened clinical attention and research addressing symptom course specifiers. Continued efforts are needed to refine the diagnostic and prognostic accuracy of PRSs in mental healthcare.eng
dc.description.indexMEDLINEeng
dc.description.sponsorshipZurich Program for Sustainable Development of Mental Health Services (ZInEP)
dc.description.sponsorshipDonald C. Cooper-Fonds
dc.description.sponsorshipGerman Research Foundation (DFG)German Research Foundation (DFG) [FOR2107, WI 3439/3-2, GRK 2350]
dc.description.sponsorshipGerman Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMentFederal Ministry of Education & Research (BMBF) [01ZX1614K, 01ZX1614G, 01ZX1614A]
dc.description.sponsorshipGerman Federal Ministry of Education and Research (BMBF)Federal Ministry of Education & Research (BMBF) [ASD-Net (01EE1409C), 01EE1406C, 01EW1904, 01EW1810, 031L0190A, 01ZX01909A]
dc.description.sponsorshipDr. Lisa Oehler Foundation
dc.description.sponsorshipKassel (Germany)
dc.description.sponsorshipInterdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Munster [Dan3/012/17]
dc.description.sponsorshipBONFOR Programme of the University of Bonn, Germany
dc.description.sponsorshipElse Kroner-Fresenius-Stiftung [2019_A127]
dc.description.sponsorshipEuropean Union's Horizon 2020 Research and Innovation Programme (PSY-PGx) [945151]
dc.description.sponsorshipMunich Clinician Scientist Program (MCSP)
dc.description.sponsorshipSwiss National Science Foundation (SNSF)Swiss National Science Foundation (SNSF)
dc.description.sponsorshipHSM High Specialized Medicine of the Canton Zurich, Switzerland
dc.description.sponsorshipHartmann Muller Foundation
dc.description.sponsorshipOlga Mayenfisch Foundation
dc.description.sponsorshipGertrud Thalmann Foundation
dc.description.sponsorshipClinician Scientist Programme of the Medical Faculty of Ulm University
dc.description.sponsorshipIlidio Pinho professorship and iBiMED [UID/BIM/04501/2013]
dc.identifier.citationTRANSLATIONAL PSYCHIATRY, v.11, n.1, article ID 600, 11p, 2021
dc.identifier.doi10.1038/s41398-021-01720-0
dc.identifier.issn2158-3188
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/44239
dc.language.isoeng
dc.publisherSPRINGERNATUREeng
dc.relation.ispartofTranslational Psychiatry
dc.rightsopenAccesseng
dc.rights.holderCopyright SPRINGERNATUREeng
dc.subject.otherclinical high-riskeng
dc.subject.otherbipolar disordereng
dc.subject.otherfuture-directionseng
dc.subject.othergenetic riskeng
dc.subject.otherschizophreniaeng
dc.subject.otherschizotypyeng
dc.subject.othercontinuumeng
dc.subject.otherassociationeng
dc.subject.othertransitioneng
dc.subject.othersalienceeng
dc.subject.wosPsychiatryeng
dc.titlePolygenic risk scores across the extended psychosis spectrumeng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.affiliation.countrySuíça
hcfmusp.affiliation.countryAlemanha
hcfmusp.affiliation.countryAustrália
hcfmusp.affiliation.countryÁustria
hcfmusp.affiliation.countryPortugal
hcfmusp.affiliation.countryEstados Unidos
hcfmusp.affiliation.countryisode
hcfmusp.affiliation.countryisoch
hcfmusp.affiliation.countryisoau
hcfmusp.affiliation.countryisoat
hcfmusp.affiliation.countryisopt
hcfmusp.affiliation.countryisous
hcfmusp.author.externalSMIGIELSKI, Lukasz:Univ Zurich, Psychiat Univ Hosp Zurich, Dept Child & Adolescent Psychiat & Psychotherapy, Zurich, Switzerland; Psychiat Univ Hosp Zurich, Zurich Program Sustainable Dev Mental Hlth Serv, Zurich, Switzerland
hcfmusp.author.externalPAPIOL, Sergi:Ludwig Maximilians Univ Munchen, Inst Psychiat Phen & Genom IPPG, Univ Hosp, Munich, Germany; Ludwig Maximilians Univ Munchen, Dept Psychiat & Psychotherapy, Univ Hosp, Munich, Germany
hcfmusp.author.externalTHEODORIDOU, Anastasia:Psychiat Univ Hosp Zurich, Zurich Program Sustainable Dev Mental Hlth Serv, Zurich, Switzerland; Univ Zurich, Psychiat Univ Hosp Zurich, Dept Psychiat Psychotherapy & Psychosomat, Zurich, Switzerland
hcfmusp.author.externalHEEKEREN, Karsten:Psychiat Univ Hosp Zurich, Zurich Program Sustainable Dev Mental Hlth Serv, Zurich, Switzerland; Univ Zurich, Psychiat Univ Hosp Zurich, Dept Psychiat Psychotherapy & Psychosomat, Zurich, Switzerland; LVR Hosp, Dept Psychiat & Psychotherapy 1, Cologne, Germany
hcfmusp.author.externalGERSTENBERG, Miriam:Univ Zurich, Psychiat Univ Hosp Zurich, Dept Child & Adolescent Psychiat & Psychotherapy, Zurich, Switzerland; Psychiat Univ Hosp Zurich, Zurich Program Sustainable Dev Mental Hlth Serv, Zurich, Switzerland
hcfmusp.author.externalWOTRUBA, Diana:Psychiat Univ Hosp Zurich, Zurich Program Sustainable Dev Mental Hlth Serv, Zurich, Switzerland
hcfmusp.author.externalBUECHLER, Roman:Psychiat Univ Hosp Zurich, Zurich Program Sustainable Dev Mental Hlth Serv, Zurich, Switzerland; Univ Hosp Zurich, Dept Neuroradiol, Zurich, Switzerland
hcfmusp.author.externalHOFFMANN, Per:Univ Hosp, Dept Biomed, HumanGen Res Grp, Basel, Switzerland; Univ Basel, Basel, Switzerland; Univ Bonn, Sch Med, Inst Human Genet, Bonn, Germany; Univ Hosp Bonn, Bonn, Germany
hcfmusp.author.externalHERMS, Stefan:Univ Hosp, Dept Biomed, HumanGen Res Grp, Basel, Switzerland; Univ Basel, Basel, Switzerland; Univ Bonn, Sch Med, Inst Human Genet, Bonn, Germany; Univ Hosp Bonn, Bonn, Germany
hcfmusp.author.externalADORJAN, Kristina:Ludwig Maximilians Univ Munchen, Inst Psychiat Phen & Genom IPPG, Univ Hosp, Munich, Germany; Ludwig Maximilians Univ Munchen, Dept Psychiat & Psychotherapy, Univ Hosp, Munich, Germany
hcfmusp.author.externalANDERSON-SCHMIDT, Heike:Univ Med Ctr Gottingen, Dept Psychiat & Psychotherapy, Gottingen, Germany
hcfmusp.author.externalBUDDE, Monika:Ludwig Maximilians Univ Munchen, Inst Psychiat Phen & Genom IPPG, Univ Hosp, Munich, Germany
hcfmusp.author.externalCOMES, Ashley L.:Ludwig Maximilians Univ Munchen, Inst Psychiat Phen & Genom IPPG, Univ Hosp, Munich, Germany; Max Planck Inst Psychiat, Int Max Planck Res Sch Translat Psychiat, Munich, Germany
hcfmusp.author.externalGADE, Katrin:Univ Med Ctr Gottingen, Dept Psychiat & Psychotherapy, Gottingen, Germany
hcfmusp.author.externalHEILBRONNER, Maria:Ludwig Maximilians Univ Munchen, Inst Psychiat Phen & Genom IPPG, Univ Hosp, Munich, Germany
hcfmusp.author.externalHEILBRONNER, Urs:Ludwig Maximilians Univ Munchen, Inst Psychiat Phen & Genom IPPG, Univ Hosp, Munich, Germany
hcfmusp.author.externalKALMAN, Janos L.:Ludwig Maximilians Univ Munchen, Inst Psychiat Phen & Genom IPPG, Univ Hosp, Munich, Germany; Ludwig Maximilians Univ Munchen, Dept Psychiat & Psychotherapy, Univ Hosp, Munich, Germany; Max Planck Inst Psychiat, Int Max Planck Res Sch Translat Psychiat, Munich, Germany
hcfmusp.author.externalKLOEHN-SAGHATOLISLAM, Farahnaz:Ludwig Maximilians Univ Munchen, Inst Psychiat Phen & Genom IPPG, Univ Hosp, Munich, Germany
hcfmusp.author.externalREICH-ERKELENZ, Daniela:Ludwig Maximilians Univ Munchen, Inst Psychiat Phen & Genom IPPG, Univ Hosp, Munich, Germany; Ludwig Maximilians Univ Munchen, Dept Psychiat & Psychotherapy, Univ Hosp, Munich, Germany
hcfmusp.author.externalSCHAUPP, Sabrina K.:Ludwig Maximilians Univ Munchen, Inst Psychiat Phen & Genom IPPG, Univ Hosp, Munich, Germany
hcfmusp.author.externalSCHULTE, Eva C.:Ludwig Maximilians Univ Munchen, Inst Psychiat Phen & Genom IPPG, Univ Hosp, Munich, Germany; Ludwig Maximilians Univ Munchen, Dept Psychiat & Psychotherapy, Univ Hosp, Munich, Germany
hcfmusp.author.externalSENNER, Fanny:Ludwig Maximilians Univ Munchen, Inst Psychiat Phen & Genom IPPG, Univ Hosp, Munich, Germany; Ludwig Maximilians Univ Munchen, Dept Psychiat & Psychotherapy, Univ Hosp, Munich, Germany
hcfmusp.author.externalANGHELESCU, Ion-George:Mental Hlth Inst, Dept Psychiat & Psychotherapy, Berlin, Germany
hcfmusp.author.externalAROLT, Volker:Univ Munster, Inst Translat Psychiat, Munster, Germany
hcfmusp.author.externalBAUNE, Bernhard T.:Univ Munster, Dept Psychiat, Munster, Germany; Univ Melbourne, Melbourne Med Sch, Dept Psychiat, Melbourne, Vic, Australia; Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic, Australia
hcfmusp.author.externalDANNLOWSKI, Udo:Univ Munster, Inst Translat Psychiat, Munster, Germany
hcfmusp.author.externalDIETRICH, Detlef E.:AMEOS Clin Ctr Hildesheim, Hildesheim, Germany; Ctr Syst Neurosci ZSN, Hannover, Germany
hcfmusp.author.externalFALLGATTER, Andreas J.:Univ Tubingen, Tubingen Ctr Mental Hlth TuCMH, Dept Psychiat & Psychotherapy, Tubingen, Germany
hcfmusp.author.externalFIGGE, Christian:European Med Sch Oldenburg Groningen, Karl Jaspers Clin, Oldenburg, Germany
hcfmusp.author.externalJAEGER, Markus:Ulm Univ, Dept Psychiat 2, Bezirkskrankenhaus Gunzburg, Gunzburg, Germany
hcfmusp.author.externalJUCKEL, Georg:Ruhr Univ Bochum, LWL Univ Hosp, Dept Psychiat, Bochum, Germany
hcfmusp.author.externalKONRAD, Carsten:Agaplesion Diakonieklinikum, Dept Psychiat & Psychotherapy, Rotenburg, Germany
hcfmusp.author.externalNIERATSCHKER, Vanessa:Univ Tubingen, Tubingen Ctr Mental Hlth TuCMH, Dept Psychiat & Psychotherapy, Tubingen, Germany
hcfmusp.author.externalREIMER, Jens:Klinikum Bremen Ost, Dept Psychiat, Bremen, Germany; Univ Med Ctr Hamburg Eppendorf, Dept Psychiat, Hamburg, Germany
hcfmusp.author.externalREININGHAUS, Eva:Med Univ Graz, Dept Psychiat & Psychotherapeut Med, Res Unit Bipolar Affect Disorder, Graz, Austria
hcfmusp.author.externalSCHMAUSS, Max:Augsburg Univ, Med Fac, Bezirkskrankenhaus Augsburg, Clin Psychiat Psychotherapy & Psychosomat, Augsburg, Germany
hcfmusp.author.externalSPITZER, Carsten:Univ Med Ctr Rostock, Dept Psychosomat Med & Psychotherapy, Rostock, Germany
hcfmusp.author.externalHAGEN, Martin von:Clin Ctr Werra Meissner, Clin Psychiat & Psychotherapy, Eschwege, Germany
hcfmusp.author.externalWILTFANG, Jens:Univ Med Ctr Gottingen, Dept Psychiat & Psychotherapy, Gottingen, Germany; German Ctr Neurodegenerat Dis DZNE, Gottingen, Germany; Univ Aveiro, Med Sci Dept, iBiMED, Aveiro, Portugal
hcfmusp.author.externalZIMMERMANN, Joerg:Psychiat Verbund Oldenburger Land gGmbH, Karl Jaspers Klin, Bad Zwischenahn, Germany
hcfmusp.author.externalGRYAZNOVA, Anna:Ludwig Maximilians Univ Munchen, Inst Psychiat Phen & Genom IPPG, Univ Hosp, Munich, Germany
hcfmusp.author.externalFLATAU-NAGEL, Laura:Ludwig Maximilians Univ Munchen, Inst Psychiat Phen & Genom IPPG, Univ Hosp, Munich, Germany
hcfmusp.author.externalREITT, Markus:Univ Med Ctr Gottingen, Dept Psychiat & Psychotherapy, Gottingen, Germany
hcfmusp.author.externalMEYERS, Milena:Ruhr Univ Bochum, LWL Univ Hosp, Dept Psychiat, Bochum, Germany
hcfmusp.author.externalEMONS, Barbara:Ruhr Univ Bochum, LWL Univ Hosp, Dept Psychiat, Bochum, Germany
hcfmusp.author.externalHAUSSLEITER, Ida Sybille:Ruhr Univ Bochum, LWL Univ Hosp, Dept Psychiat, Bochum, Germany
hcfmusp.author.externalLANG, Fabian U.:Ulm Univ, Dept Psychiat 2, Bezirkskrankenhaus Gunzburg, Gunzburg, Germany
hcfmusp.author.externalBECKER, Thomas:Ulm Univ, Dept Psychiat 2, Bezirkskrankenhaus Gunzburg, Gunzburg, Germany
hcfmusp.author.externalWIGAND, Moritz E.:Ulm Univ, Dept Psychiat 2, Bezirkskrankenhaus Gunzburg, Gunzburg, Germany
hcfmusp.author.externalWITT, Stephanie H.:Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany
hcfmusp.author.externalDEGENHARDT, Franziska:Univ Bonn, Sch Med, Inst Human Genet, Bonn, Germany; Univ Hosp Bonn, Bonn, Germany
hcfmusp.author.externalFORSTNER, Andreas J.:Univ Bonn, Sch Med, Inst Human Genet, Bonn, Germany; Univ Hosp Bonn, Bonn, Germany; Univ Marburg, Ctr Human Genet, Marburg, Germany; Res Ctr Julich, Inst Neurosci & Med INM 1, Julich, Germany
hcfmusp.author.externalRIETSCHEL, Marcella:Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany
hcfmusp.author.externalNOTHEN, Markus M.:Univ Bonn, Sch Med, Inst Human Genet, Bonn, Germany; Univ Hosp Bonn, Bonn, Germany
hcfmusp.author.externalANDLAUER, Till F. M.:Tech Univ Munich, Sch Med, Dept Neurol, Klinikum rechts Isar, Munich, Germany
hcfmusp.author.externalWALITZA, Susanne:Univ Zurich, Psychiat Univ Hosp Zurich, Dept Child & Adolescent Psychiat & Psychotherapy, Zurich, Switzerland; Univ Zurich, Neurosci Ctr Zurich, Zurich, Switzerland; Swiss Fed Inst Technol, Zurich, Switzerland; Univ Zurich, Zurich Ctr Integrat Human Physiol, Zurich, Switzerland
hcfmusp.author.externalFALKAI, Peter:Ludwig Maximilians Univ Munchen, Dept Psychiat & Psychotherapy, Univ Hosp, Munich, Germany
hcfmusp.author.externalSCHULZE, Thomas G.:Ludwig Maximilians Univ Munchen, Inst Psychiat Phen & Genom IPPG, Univ Hosp, Munich, Germany; SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY 13210 USA; Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA
hcfmusp.author.externalGRUENBLATT, Edna:Univ Zurich, Psychiat Univ Hosp Zurich, Dept Child & Adolescent Psychiat & Psychotherapy, Zurich, Switzerland; Univ Zurich, Neurosci Ctr Zurich, Zurich, Switzerland; Swiss Fed Inst Technol, Zurich, Switzerland; Univ Zurich, Zurich Ctr Integrat Human Physiol, Zurich, Switzerland
hcfmusp.citation.scopus9
hcfmusp.description.articlenumber600
hcfmusp.description.issue1
hcfmusp.description.volume11
hcfmusp.origemWOS
hcfmusp.origem.pubmed34836939
hcfmusp.origem.scopus2-s2.0-85119973325
hcfmusp.origem.wosWOS:000722844000001
hcfmusp.publisher.cityLONDONeng
hcfmusp.publisher.countryENGLANDeng
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