Polygenic risk scores enhance prediction of body mass index increase in individuals with a first episode of psychosis

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• dc.contributor.author Muntané, Gerard
• dc.contributor.author Vázquez-Bourgon, Javier
• dc.contributor.author Sada, Ester
• dc.contributor.author Martorell, Lourdes
• dc.contributor.author Papiol, Sergi
• dc.contributor.author Bosch Fusté, Elena
• dc.contributor.author Navarro i Cuartiellas, Arcadi, 1969-
• dc.contributor.author Crespo-Facorro, Benedicto
• dc.contributor.author Vilella, Elisabet
• dc.date.accessioned 2023-06-08T06:48:59Z
• dc.date.available 2023-06-08T06:48:59Z
• dc.date.issued 2023
• dc.description.abstract Background: Individuals with a first episode of psychosis (FEP) show rapid weight gain during the first months of treatment, which is associated with a reduction in general physical health. Although genetics is assumed to be a significant contributor to weight gain, its exact role is unknown. Methods: We assembled a population-based FEP cohort of 381 individuals that was split into a Training (n = 224) set and a Validation (n = 157) set to calculate the polygenic risk score (PRS) in a two-step process. In parallel, we obtained reference genome-wide association studies for body mass index (BMI) and schizophrenia (SCZ) to examine the pleiotropic landscape between the two traits. BMI PRSs were added to linear models that included sociodemographic and clinical variables to predict BMI increase (∆BMI) in the Validation set. Results: The results confirmed considerable shared genetic susceptibility for the two traits involving 449 near-independent genomic loci. The inclusion of BMI PRSs significantly improved the prediction of ∆BMI at 12 months after the onset of antipsychotic treatment by 49.4% compared to a clinical model. In addition, we demonstrated that the PRS containing pleiotropic information between BMI and SCZ predicted ∆BMI better at 3 (12.2%) and 12 months (53.2%). Conclusions: We prove for the first time that genetic factors play a key role in determining ∆BMI during the FEP. This finding has important clinical implications for the early identification of individuals most vulnerable to weight gain and highlights the importance of examining genetic pleiotropy in the context of medically important comorbidities for predicting future outcomes.
• dc.description.sponsorship This work was supported by the Catalan Agency of Research and Universities (AGAUR, 2017SGR-00444, PI: E.V.). G.M. is supported by Instituto de Salud Carlos III (PI18/00514 and PI21/00612). The Santander (PAFIP) cohort was funded by the following grants: Instituto de Salud Carlos III (FIS00/3095, PI020499, PI050427, PI060507), Plan Nacional de Drogas Research (2005-Orden sco/3246/2004), SENY Fundatio Research (2005-0308007), Fundacion Marques de Valdecilla (A/02/07, API07/011), and MINECO/FEDER (SAF2016-76046-R, SAF2013-46292-R). J.V.-B. is supported by funding from Instituto de Investigación Valdecilla (INT/A21/10, INT/A20/04). A.N. is supported by funding from AEI-PGC2018-BI00 (FEDER/UE) (MINECO/FEDER, UE), “Unidad de Excelencia María de Maeztu,” funded by the AEI (CEX2018-000792-M), Secretaria d’Universitats i Recerca, and the CERCA Program of the Departament d’Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 SGR 880).
• dc.format.mimetype application/pdf
• dc.identifier.citation Muntané G, Vázquez-Bourgon J, Sada E, Martorell L, Papiol S, Bosch E, Navarro A, Crespo-Facorro B, Vilella E. Polygenic risk scores enhance prediction of body mass index increase in individuals with a first episode of psychosis. Eur Psychiatr. 2023;66(1):e28. DOI: 10.1192/j.eurpsy.2023.9
• dc.identifier.doi http://dx.doi.org/10.1192/j.eurpsy.2023.9
• dc.identifier.issn 0924-9338
• dc.identifier.uri http://hdl.handle.net/10230/57111
• dc.language.iso eng
• dc.publisher Cambridge University Press
• dc.relation.ispartof Eur Psychiatr. 2023;66(1):e28
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-76046-R
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2013-46292-R
• dc.rights © The Author(s), 2023. Published by Cambridge University Press on behalf of the European Psychiatric Association. This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0
• dc.subject.keyword BMI
• dc.subject.keyword First-episode psychosis
• dc.subject.keyword Pleiotropy
• dc.subject.keyword Polygenic risk scores
• dc.subject.keyword Weight gain
• dc.title Polygenic risk scores enhance prediction of body mass index increase in individuals with a first episode of psychosis
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion