Polygenic risk scores across the extended psychosis spectrum

• DOI: 10.1038/s41398-021-01720-0
• Publication Date: 2021-11-26T11:02:47Z
• Authors: Lukasz Smigielski; Sergi Papiol; Anastasia Theodor...; Karsten Heekeren; Miriam Gerstenberg; Diana Wotruba; Roman Buechler; Per Hoffmann; Stefan Herms; Kristina Adorjan; Heike Anderson-Sc...; Monika Budde; Ashley L. Comes; Katrin Gade; Maria Heilbronner; Urs Heilbronner; Janos L. Kalman; Farahnaz Klöhn-Sa...; Daniela Reich-Erk...; Sabrina K. Schaupp; Eva C. Schulte; Fanny Senner; Ion-George Anghel...; Volker Arolt; Bernhard T. Baune; Udo Dannlowski; Detlef E. Dietrich; Andreas J. Fallga...; Christian Figge; Markus Jäger; Georg Juckel; Carsten Konrad; Vanessa Nieratschker; Jens Reimer; Eva Reininghaus; Max Schmauß; Carsten Spitzer; Martin von Hagen; Jens Wiltfang; Jörg Zimmermann; Anna Gryaznova; Laura Flatau-Nagel; Markus Reitt; Milena Meyers; Barbara Emons; Ida Sybille Haußl...; Fabian U. Lang; Thomas Becker; Moritz E. Wigand; Stephanie H. Witt; Franziska Degenhardt; Andreas J. Forstner; Marcella Rietschel; Markus M. Nöthen; Till F. M. Andlauer; Wulf Rössler; Susanne Walitza; Peter Falkai; Thomas G. Schulze; Edna Grünblatt
• Keywords: Bonferroni correction; Subclinical infection

Abstract As early detection of symptoms in the subclinical to clinical psychosis spectrum may improve health outcomes, knowing probabilistic susceptibility developing a disorder could guide mitigation measures and intervention. In this context, polygenic risk scores (PRSs) quantifying additive effects multiple common genetic variants hold potential predict complex diseases index severity gradients. PRSs for schizophrenia (SZ) bipolar (BD) were computed using Bayesian regression continuous shrinkage priors based on latest SZ BD genome-wide association studies (Psychiatric Genomics Consortium, third release). Eight well-phenotyped groups ( n = 1580; 56% males) assessed: control 305), lower 117) higher 113) schizotypy (both healthy individuals), at-risk 120), type-I 359), type-II 96), schizoaffective 86), 384). PRS differences investigated binary traits quantitative Positive Negative Syndrome Scale. Both BD-PRS SZ-PRS significantly differentiated controls from (Nagelkerke’s pseudo- R 2 : 1.3–7.7%), except SZ-PRS. Out 28 pairwise comparisons BD-PRS, 9 12, respectively, reached Bonferroni-corrected significance. differed between groups, but not groups. There was no difference schizotypy. SZ-PRSs, BD-PRSs, positively associated with transdiagnostic symptomology. Overall, support continuum model across at genomic level possible irregularities The state demands heightened attention research addressing symptom course specifiers. Continued efforts are needed refine diagnostic prognostic accuracy mental healthcare.