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dc.contributor.authorSteen, Nils Eiel
dc.contributor.authorRahman, Zillur
dc.contributor.authorSzabo, Attila
dc.contributor.authorHindley, Guy
dc.contributor.authorParker, Nadine
dc.contributor.authorCheng, Weiqiu
dc.contributor.authorLin, Aihua
dc.contributor.authorO'Connell, Kevin S
dc.contributor.authorSheikh, Mashhood Ahmed
dc.contributor.authorShadrin, Alexey
dc.contributor.authorBahrami, Shahram
dc.contributor.authorKarthikeyan, Sandeep
dc.contributor.authorHoseth, Eva Zsuzsanna
dc.contributor.authorDale, Anders M
dc.contributor.authorAukrust, Pål
dc.contributor.authorSmeland, Olav Bjerkehagen
dc.contributor.authorUeland, Thor
dc.contributor.authorFrei, Oleksandr
dc.contributor.authorDjurovic, Srdjan
dc.contributor.authorAndreassen, Ole
dc.date.accessioned2023-12-11T12:10:11Z
dc.date.available2023-12-11T12:10:11Z
dc.date.issued2023-06-15
dc.description.abstractBackground - Immune mechanisms are indicated in schizophrenia (SCZ). Recent genome-wide association studies (GWAS) have identified genetic variants associated with SCZ and immune-related phenotypes. Here, we use cutting edge statistical tools to identify shared genetic variants between SCZ and white blood cell (WBC) counts and further understand the role of the immune system in SCZ.<p> <p>Study Design - GWAS results from SCZ (patients, n = 53 386; controls, n = 77 258) and WBC counts (n = 56 3085) were analyzed. We applied linkage disequilibrium score regression, the conditional false discovery rate method and the bivariate causal mixture model for analyses of genetic associations and overlap, and 2 sample Mendelian randomization to estimate causal effects.<p> <p>Study Results - The polygenicity for SCZ was 7.5 times higher than for WBC count and constituted 32%–59% of WBC count genetic loci. While there was a significant but weak positive genetic correlation between SCZ and lymphocytes (rg = 0.05), the conditional false discovery rate method identified 383 shared genetic loci (53% concordant effect directions), with shared variants encompassing all investigated WBC subtypes: lymphocytes, n = 215 (56% concordant); neutrophils, n = 158 (49% concordant); monocytes, n = 146 (47% concordant); eosinophils, n = 135 (56% concordant); and basophils, n = 64 (53% concordant). A few causal effects were suggested, but consensus was lacking across different Mendelian randomization methods. Functional analyses indicated cellular functioning and regulation of translation as overlapping mechanisms.<p> <p>Conclusions - Our results suggest that genetic factors involved in WBC counts are associated with the risk of SCZ, indicating a role of immune mechanisms in subgroups of SCZ with potential for stratification of patients for immune targeted treatment.en_US
dc.identifier.citationSteen, Rahman, Szabo, Hindley, Parker, Cheng, Lin, O'Connell, Sheikh, Shadrin, Bahrami, Karthikeyan, Hoseth, Dale, Aukrust, Smeland, Ueland, Frei, Djurovic, Andreassen. Shared Genetic Loci Between Schizophrenia and White Blood Cell Counts Suggest Genetically Determined Systemic Immune Abnormalities. Schizophrenia Bulletin. 2023;49(5):1345-1354en_US
dc.identifier.cristinIDFRIDAID 2189083
dc.identifier.doi10.1093/schbul/sbad082
dc.identifier.issn0586-7614
dc.identifier.issn1745-1701
dc.identifier.urihttps://hdl.handle.net/10037/31992
dc.language.isoengen_US
dc.publisherOxford University Pressen_US
dc.relation.journalSchizophrenia Bulletin
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/847776/Norway/Predicting comorbid cardiovascular disease in individuals with mental disorder by decoding disease mechanisms/CoMorMent/en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/964874/Norway/Using real-world big data from eHealth, biobanks and national registries, integrated with clinical trial data to improve outcome of severe mental disorders/REALMENT/en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2023 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0en_US
dc.rightsAttribution-NonCommercial 4.0 International (CC BY-NC 4.0)en_US
dc.titleShared Genetic Loci Between Schizophrenia and White Blood Cell Counts Suggest Genetically Determined Systemic Immune Abnormalitiesen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
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