Polygenic risk scores across the extended psychosis spectrum
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) quantifyin...
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Nature Publishing Group
2021
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oai:doaj.org-article:057a8222a0e64555a64d03d86616addf2021-11-28T12:09:28ZPolygenic risk scores across the extended psychosis spectrum10.1038/s41398-021-01720-02158-3188https://doaj.org/article/057a8222a0e64555a64d03d86616addf2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41398-021-01720-0https://doaj.org/toc/2158-3188Abstract 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-R 2: 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.Lukasz SmigielskiSergi PapiolAnastasia TheodoridouKarsten HeekerenMiriam GerstenbergDiana WotrubaRoman BuechlerPer HoffmannStefan HermsKristina AdorjanHeike Anderson-SchmidtMonika BuddeAshley L. ComesKatrin GadeMaria HeilbronnerUrs HeilbronnerJanos L. KalmanFarahnaz Klöhn-SaghatolislamDaniela Reich-ErkelenzSabrina K. SchauppEva C. SchulteFanny SennerIon-George AnghelescuVolker AroltBernhard T. BauneUdo DannlowskiDetlef E. DietrichAndreas J. FallgatterChristian FiggeMarkus JägerGeorg JuckelCarsten KonradVanessa NieratschkerJens ReimerEva ReininghausMax SchmaußCarsten SpitzerMartin von HagenJens WiltfangJörg ZimmermannAnna GryaznovaLaura Flatau-NagelMarkus ReittMilena MeyersBarbara EmonsIda Sybille HaußleiterFabian U. LangThomas BeckerMoritz E. WigandStephanie H. WittFranziska DegenhardtAndreas J. ForstnerMarcella RietschelMarkus M. NöthenTill F. M. AndlauerWulf RösslerSusanne WalitzaPeter FalkaiThomas G. SchulzeEdna GrünblattNature Publishing GrouparticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENTranslational Psychiatry, Vol 11, Iss 1, Pp 1-11 (2021) |
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DOAJ |
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EN |
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Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 |
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Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Lukasz Smigielski Sergi Papiol Anastasia Theodoridou Karsten Heekeren Miriam Gerstenberg Diana Wotruba Roman Buechler Per Hoffmann Stefan Herms Kristina Adorjan Heike Anderson-Schmidt Monika Budde Ashley L. Comes Katrin Gade Maria Heilbronner Urs Heilbronner Janos L. Kalman Farahnaz Klöhn-Saghatolislam Daniela Reich-Erkelenz Sabrina K. Schaupp Eva C. Schulte Fanny Senner Ion-George Anghelescu Volker Arolt Bernhard T. Baune Udo Dannlowski Detlef E. Dietrich Andreas J. Fallgatter 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 Haußleiter 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 Polygenic risk scores across the extended psychosis spectrum |
| description |
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-R 2: 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. |
| format |
article |
| author |
Lukasz Smigielski Sergi Papiol Anastasia Theodoridou Karsten Heekeren Miriam Gerstenberg Diana Wotruba Roman Buechler Per Hoffmann Stefan Herms Kristina Adorjan Heike Anderson-Schmidt Monika Budde Ashley L. Comes Katrin Gade Maria Heilbronner Urs Heilbronner Janos L. Kalman Farahnaz Klöhn-Saghatolislam Daniela Reich-Erkelenz Sabrina K. Schaupp Eva C. Schulte Fanny Senner Ion-George Anghelescu Volker Arolt Bernhard T. Baune Udo Dannlowski Detlef E. Dietrich Andreas J. Fallgatter 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 Haußleiter 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 |
| author_facet |
Lukasz Smigielski Sergi Papiol Anastasia Theodoridou Karsten Heekeren Miriam Gerstenberg Diana Wotruba Roman Buechler Per Hoffmann Stefan Herms Kristina Adorjan Heike Anderson-Schmidt Monika Budde Ashley L. Comes Katrin Gade Maria Heilbronner Urs Heilbronner Janos L. Kalman Farahnaz Klöhn-Saghatolislam Daniela Reich-Erkelenz Sabrina K. Schaupp Eva C. Schulte Fanny Senner Ion-George Anghelescu Volker Arolt Bernhard T. Baune Udo Dannlowski Detlef E. Dietrich Andreas J. Fallgatter 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 Haußleiter 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 |
| author_sort |
Lukasz Smigielski |
| title |
Polygenic risk scores across the extended psychosis spectrum |
| title_short |
Polygenic risk scores across the extended psychosis spectrum |
| title_full |
Polygenic risk scores across the extended psychosis spectrum |
| title_fullStr |
Polygenic risk scores across the extended psychosis spectrum |
| title_full_unstemmed |
Polygenic risk scores across the extended psychosis spectrum |
| title_sort |
polygenic risk scores across the extended psychosis spectrum |
| publisher |
Nature Publishing Group |
| publishDate |
2021 |
| url |
https://doaj.org/article/057a8222a0e64555a64d03d86616addf |
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