Polygenic risk scores across the extended psychosis spectrum.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Smigielski Lukasz, Papiol Sergi, Theodoridou Anastasia, Heekeren Karsten, Gerstenberg Miriam, Wotruba Diana, Buechler Roman, Hoffmann Per, Herms Stefan, Adorjan Kristina, Anderson-Schmidt Heike, Budde Monika, Comes Ashley L, Gade Katrin, Heilbronner Maria, Heilbronner Urs, Kalman Janos L, Klöhn-Saghatolislam Farahnaz, Reich-Erkelenz Daniela, Schaupp Sabrina K, Schulte Eva C, Senner Fanny, Anghelescu Ion-George, Arolt Volker, Baune Bernhard T, Dannlowski Udo, Dietrich Detlef E, Fallgatter Andreas J, Figge Christian, Jäger Markus, Juckel Georg, Konrad Carsten, Nieratschker Vanessa, Reimer Jens, Reininghaus Eva, Schmauß Max, Spitzer Carsten, von Hagen Martin, Wiltfang Jens, Zimmermann Jörg, Gryaznova Anna, Flatau-Nagel Laura, Reitt Markus, Meyers Milena, Emons Barbara, Haußleiter Ida Sybille, Lang Fabian U, Becker Thomas, Wigand Moritz E, Witt Stephanie H, Degenhardt Franziska, Forstner Andreas J, Rietschel Marcella, Nöthen Markus M, Andlauer Till F M, Rössler Wulf, Walitza Susanne, Falkai Peter, Schulze Thomas G, Grünblatt Edna
Аннотация
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.