Use of multiple polygenic risk scores for distinguishing schizophrenia-spectrum disorder and affective psychosis categories in a first-episode sample; the EU-GEI study - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Psychological Medicine Année : 2022

Use of multiple polygenic risk scores for distinguishing schizophrenia-spectrum disorder and affective psychosis categories in a first-episode sample; the EU-GEI study

1 Institute of Psychiatry, Psychology & Neuroscience, King's College London
2 Universidad de Sevilla = University of Seville
3 Hospital Universitario Virgen del Rocío [Sevilla]
4 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
5 UNIROMA - Università degli Studi di Roma "La Sapienza" = Sapienza University [Rome]
6 Università degli studi di Palermo - University of Palermo
7 UCL - University College of London [London]
8 MHAS - Mental Health and Addiction Services, ASP Crotone [Crotone, Italy]
9 UNIVR - Università degli studi di Verona = University of Verona
10 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
11 U955 Inserm - UPEC - IMRB - "Neuropsychiatrie translationnelle" [Créteil]
12 MUMC - Maastricht University Medical Centre
13 GGZ Rivierduinen - Rivierduinen Institute for Mental Health Care [Leiden, Netherlands]
14 MSSM - Icahn School of Medicine at Mount Sinai [New York]
15 Amsterdam UMC - Amsterdam University Medical Center
16 UvA - University of Amsterdam [Amsterdam] = Universiteit van Amsterdam
17 UCA - Université Clermont Auvergne
18 IDIS - Instituto de Investigación Sanitaria de Santiago de Compostela / Health Research Institute of Santiago de Compostela
19 CHUS - Complejo Hospitalario Universitario de Santiago de Compostela [Saint-Jacques-de-Compostelle, Espagne]
20 University of Oviedo
21 CIBER-SAM - Centro de Investigación Biomédica en Red Salud Mental [Madrid]
22 ISPA - Instituto de Investigación Sanitaria del Principado de Asturias [Oviedo, Spain]
23 Clinic Barcelona Hospital Universitari
24 University of Barcelona
25 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
26 UCM - Universidad Complutense de Madrid = Complutense University of Madrid [Madrid]
27 Hospital General Universitario "Gregorio Marañón" [Madrid]
28 IiSGM - Instituto de Investigación Sanitaria Gregorio Marañón [Madrid, Spain]
29 CAM - University of Cambridge [UK]
30 CPFT - Cambridgeshire & Peterborough NHS Foundation Trust [Cambridge]
31 Cardiff University
32 HKU - The University of Hong Kong
33 Li Kashing Faculty of Medicine [Hong Kong]
34 University Medical Center [Utrecht]

Résumé

Background: Schizophrenia (SZ), bipolar disorder (BD) and depression (D) run in families. This susceptibility is partly due to hundreds or thousands of common genetic variants, each conferring a fractional risk. The cumulative effects of the associated variants can be summarised as a polygenic risk score (PRS). Using data from the EUropean Network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) first episode case-control study, we aimed to test whether PRSs for three major psychiatric disorders (SZ, BD, D) and for intelligent quotient (IQ) as a neurodevelopmental proxy, can discriminate affective psychosis (AP) from schizophrenia-spectrum disorder (SSD). Methods: Participants (842 cases, 1284 controls) from 16 European EU-GEI sites were successfully genotyped following standard quality control procedures. The sample was stratified based on genomic ancestry and analyses were done only on the subsample representing the European population (573 cases, 1005 controls). Using PRS for SZ, BD, D, and IQ built from the latest available summary statistics, we performed simple or multinomial logistic regression models adjusted for 10 principal components for the different clinical comparisons. Results: In case-control comparisons PRS-SZ, PRS-BD and PRS-D distributed differentially across psychotic subcategories. In case-case comparisons, both PRS-SZ [odds ratio (OR) = 0.7, 95% confidence interval (CI) 0.54-0.92] and PRS-D (OR = 1.31, 95% CI 1.06-1.61) differentiated AP from SSD; and within AP categories, only PRS-SZ differentiated BD from psychotic depression (OR = 2.14, 95% CI 1.23-3.74). Conclusions: Combining PRS for severe psychiatric disorders in prediction models for psychosis phenotypes can increase discriminative ability and improve our understanding of these phenotypes. Our results point towards the potential usefulness of PRSs in specific populations such as high-risk or early psychosis phases.
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Origine : Publication financée par une institution
Licence : CC BY - Paternité

Dates et versions

inserm-04197682 , version 1 (06-09-2023)

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Victoria Rodriguez, Luis Alameda, Diego Quattrone, Giada Tripoli, Charlotte Gayer-Anderson, et al.. Use of multiple polygenic risk scores for distinguishing schizophrenia-spectrum disorder and affective psychosis categories in a first-episode sample; the EU-GEI study. Psychological Medicine, 2022, 53 (8), pp.3396 - 3405. ⟨10.1017/s0033291721005456⟩. ⟨inserm-04197682⟩
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