Polygenic risk score analyses of symptoms and treatment response in an antipsychotic-naive first episode of psychosis cohort

Translational Psychiatry
Marcos Leite SantoroG Breen

Abstract

In this study, we aimed to test if the schizophrenia (SCZ) polygenic risk score (PRS) was associated with clinical symptoms in (a) the first episode of psychosis pre-treatment (FEP), (b) at nine weeks after initiation of risperidone treatment (FEP-9W) and (c) with the response to risperidone. We performed a detailed clinical assessment of 60 FEP patients who were antipsychotic-naive and, again, after nine weeks of standardized treatment with risperidone. After blood collection and DNA isolation, the samples were genotyped using the Illumina PsychArrayChip and then imputed. To calculate PRS, we used the latest available GWAS summary statistics from the Psychiatric Genomics Consortium wave-2 SCZ group as a training set. We used Poisson regression to test association between PRS and clinical measurements correcting for the four principal components (genotyping). We considered a p-value < 0.0014 (Bonferroni correction) as significant. First, we verified that the schizophrenia PRS was also able to distinguish cases from controls in this south-eastern Brazilian sample, with a similar variance explained to that seen in Northern European populations. In addition, within-cases analyses, we found that PRS is significantly correlated with...Continue Reading

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Citations

May 6, 2020·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Bettina MeiserTatiane Yanes
Jun 14, 2019·Frontiers in Pharmacology·Claudia Pisanu, Alessio Squassina
Jul 28, 2020·Nature Protocols·Shing Wan ChoiPaul F O'Reilly
Feb 10, 2021·Pharmaceuticals·Yerye Gibrán Mayén-LoboNancy Monroy-Jaramillo
Mar 20, 2021·European Psychiatry : the Journal of the Association of European Psychiatrists·Gamze ErzinSinan Guloksuz
May 29, 2021·Schizophrenia Research·Amanda J LisowayJames L Kennedy
May 28, 2021·Frontiers in Psychiatry·Humberto NicoliniMaría Elena Medina-Mora
Oct 14, 2021·Expert Opinion on Drug Metabolism & Toxicology·Maike Scherf-ClavelAngelika Erhardt-Lehmann
Nov 28, 2021·Translational Psychiatry·Lukasz SmigielskiEdna Grünblatt
Dec 26, 2021·Clinical Pharmacology and Therapeutics·Danielle JohnsonBritt I Drögemöller

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Methods Mentioned

BETA
genotyping

Software Mentioned

plink1
PRSice

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