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@ARTICLE{Smigielski:903471,
author = {Smigielski, Lukasz and Papiol, Sergi and Theodoridou,
Anastasia and Heekeren, Karsten and Gerstenberg, Miriam and
Wotruba, Diana and Buechler, Roman and Hoffmann, Per and
Herms, Stefan and Adorjan, Kristina and Anderson-Schmidt,
Heike and Budde, Monika and Comes, Ashley L. and Gade,
Katrin and Heilbronner, Maria and Heilbronner, Urs and
Kalman, Janos L. and Klöhn-Saghatolislam, Farahnaz and
Reich-Erkelenz, Daniela and Schaupp, Sabrina K. and Schulte,
Eva C. and Senner, Fanny and Anghelescu, Ion-George and
Arolt, Volker and Baune, Bernhard T. and Dannlowski, Udo and
Dietrich, Detlef E. and Fallgatter, Andreas J. and Figge,
Christian and Jäger, Markus and Juckel, Georg and Konrad,
Carsten and Nieratschker, Vanessa and Reimer, Jens and
Reininghaus, Eva and Schmauß, Max and Spitzer, Carsten and
von Hagen, Martin and Wiltfang, Jens and Zimmermann, Jörg
and Gryaznova, Anna and Flatau-Nagel, Laura and Reitt,
Markus and Meyers, Milena and Emons, Barbara and
Haußleiter, Ida Sybille and Lang, Fabian U. and Becker,
Thomas and Wigand, Moritz E. and Witt, Stephanie H. and
Degenhardt, Franziska and Forstner, Andreas J. and
Rietschel, Marcella and Nöthen, Markus M. and Andlauer,
Till F. M. and Rössler, Wulf and Walitza, Susanne and
Falkai, Peter and Schulze, Thomas G. and Grünblatt, Edna},
title = {{P}olygenic risk scores across the extended psychosis
spectrum},
journal = {Translational Psychiatry},
volume = {11},
number = {1},
issn = {2158-3188},
address = {London},
publisher = {Nature Publishing Group},
reportid = {FZJ-2021-05143},
pages = {600},
year = {2021},
abstract = {As 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.},
cin = {INM-1},
ddc = {610},
cid = {I:(DE-Juel1)INM-1-20090406},
pnm = {5251 - Multilevel Brain Organization and Variability
(POF4-525)},
pid = {G:(DE-HGF)POF4-5251},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34836939},
UT = {WOS:000722844000001},
doi = {10.1038/s41398-021-01720-0},
url = {https://juser.fz-juelich.de/record/903471},
}