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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 (<jats:italic>n<\/jats:italic>\u2009=\u20091580; 56% males) were assessed: control (<jats:italic>n<\/jats:italic>\u2009=\u2009305), lower (<jats:italic>n<\/jats:italic>\u2009=\u2009117) and higher (<jats:italic>n<\/jats:italic>\u2009=\u2009113) schizotypy (both groups of healthy individuals), at-risk for psychosis (<jats:italic>n<\/jats:italic>\u2009=\u2009120), BD type-I (<jats:italic>n<\/jats:italic>\u2009=\u2009359), BD type-II (<jats:italic>n<\/jats:italic>\u2009=\u200996), schizoaffective disorder (<jats:italic>n<\/jats:italic>\u2009=\u200986), and SZ groups (<jats:italic>n<\/jats:italic>\u2009=\u2009384). 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\u2019s pseudo-<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>: 1.3\u20137.7%), 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.<\/jats:p>","DOI":"10.1038\/s41398-021-01720-0","type":"journal-article","created":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T11:02:47Z","timestamp":1637924567000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Polygenic risk scores across the extended psychosis 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PF has received research support and honorarium for lectures or advisory activity from Abbott Laboratories, Boehringer Ingelheim, Janssen Pharmaceuticals, Essex Pharma, Lundbeck, Otsuka Pharmaceutical, Recordati, Richter Pharma, Servier Laboratories, and Takeda. CK has received personal fees from Aristo Pharmaceuticals, Janssen-Cilag, Eli Lilly and Company, MagVenture, Trommsdorff GmbH, Lundbeck, Neuraxpharm, and Servier Laboratories. MMN has received personal fees from the Lundbeck Foundation, the Robert-Bosch-Stiftung, HMG Systems Engineering GmbH, and Shire Deutschland GmbH. He receives salary payments from Life & Brain GmbH and holds shares in Life & Brain GmbH. JR has received personal fees from Lundbeck and Otsuka Pharmaceutical. MS has received personal fees for being a member of the speaker\u2019s bureau and advisory board from Aristo Pharmaceuticals, Janssen-Cilag, Lundbeck, Neuraxpharm, and Recordati. SW has received royalties from Thieme Hogrefe, Kohlhammer, Springer, and Beltz and lecture honoraria from Opopharma in the past 5 years. JW has received grants from the German Research Foundation and personal fees from Abbott Laboratories, Boehringer Ingelheim, Immungenetics, Eli Lilly and Company, MSD Sharp & Dohme, Roche, Actelion, Amgen, Janssen-Cilag, Pfizer, and Med Update and has patents PCT\/EP 2011001724 and PCT\/EP 2015052945 issued. The other authors declare no biomedical financial interests or potential conflicts of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"600"}}