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000903471 1001_ $$00000-0002-7428-7644$$aSmigielski, Lukasz$$b0$$eCorresponding author
000903471 245__ $$aPolygenic risk scores across the extended psychosis spectrum
000903471 260__ $$aLondon$$bNature Publishing Group$$c2021
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000903471 520__ $$aAs 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-R2: 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.
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000903471 7001_ $$aTheodoridou, Anastasia$$b2
000903471 7001_ $$aHeekeren, Karsten$$b3
000903471 7001_ $$aGerstenberg, Miriam$$b4
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000903471 7001_ $$aBuechler, Roman$$b6
000903471 7001_ $$aHoffmann, Per$$b7
000903471 7001_ $$00000-0002-2786-8200$$aHerms, Stefan$$b8
000903471 7001_ $$aAdorjan, Kristina$$b9
000903471 7001_ $$aAnderson-Schmidt, Heike$$b10
000903471 7001_ $$00000-0001-7301-9157$$aBudde, Monika$$b11
000903471 7001_ $$00000-0001-6745-9834$$aComes, Ashley L.$$b12
000903471 7001_ $$aGade, Katrin$$b13
000903471 7001_ $$aHeilbronner, Maria$$b14
000903471 7001_ $$00000-0001-7135-762X$$aHeilbronner, Urs$$b15
000903471 7001_ $$00000-0003-0930-4214$$aKalman, Janos L.$$b16
000903471 7001_ $$aKlöhn-Saghatolislam, Farahnaz$$b17
000903471 7001_ $$aReich-Erkelenz, Daniela$$b18
000903471 7001_ $$aSchaupp, Sabrina K.$$b19
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000903471 7001_ $$aBaune, Bernhard T.$$b24
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000903471 7001_ $$aFallgatter, Andreas J.$$b27
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000903471 7001_ $$00000-0001-7015-3860$$aKonrad, Carsten$$b31
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000903471 7001_ $$aMeyers, Milena$$b43
000903471 7001_ $$aEmons, Barbara$$b44
000903471 7001_ $$aHaußleiter, Ida Sybille$$b45
000903471 7001_ $$aLang, Fabian U.$$b46
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000903471 7001_ $$aNöthen, Markus M.$$b53
000903471 7001_ $$00000-0002-2917-5889$$aAndlauer, Till F. M.$$b54
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000903471 7001_ $$aSchulze, Thomas G.$$b58
000903471 7001_ $$00000-0001-8505-7265$$aGrünblatt, Edna$$b59
000903471 773__ $$0PERI:(DE-600)2609311-X$$a10.1038/s41398-021-01720-0$$gVol. 11, no. 1, p. 600$$n1$$p600$$tTranslational Psychiatry$$v11$$x2158-3188$$y2021
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