Polygenic score and transcriptomic analysis in children and teenagers at risk to psychiatric disorders

• Grant number: 16/13737-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2017
• End date: November 03, 2019
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Síntia Iole Nogueira Belangero
• Grantee: Marcos Leite Santoro
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated scholarship(s): 18/09328-2 - Evaluation of polygenic risk score performance and gene-environment interaction in an admixed Brazilian cohort, BE.EP.PD

Abstract

The objectives of this proposal are a) to improve and b) apply the polygenic risk score (PRS) to our sample of children and adolescents at risk for psychiatric disorders (PDs), c) to characterize the gene expression profile in this sample and d) compile and associate the genomic and transcriptomic results. For the PRS analysis, we will use the already genotyped samples (N = 750). For the gene expression analysis, we will select 120 children 1) major symptoms of psychopathology, measured by the Child Behavior Checklist (CBCL) and / or 2) increased genetic risk, suggested by family history for mental disorders and PRS obtained in the previous step; as well as 120 control children with lower scores for these two items and no psychiatric diagnosis. We will use the Infinum® HumanCore Array as genomic array and for the gene expression arrays the HumanHT-12 v4 Expression BeadChip. For both, we will follow the protocol recommended by the manufacturers. The analysis will be made entirely by UNIX operating systems using the command line language and the statistical program R, the PLINK and PRScise. In this study, we intend to adapt the polygenic score to our admixed Brazilian population sample and identify a gene expression profile associated with the risk for PDs. These results may help identify potential risk factors for PDs, in order to act in the future, in the early prevention and diagnosis. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SANTORO, MARCOS LEITE; OTA, VANESSA; DE JONG, SIMONE; NOTO, CRISTIANO; SPINDOLA, LETICIA M.; TALARICO, FERNANDA; GOUYEA, EDUARDO; LEE, SANG HYUCK; MORETTI, PATRICIA; CURTIS, CHARLES; et al. Polygenic risk score analyses of symptoms and treatment response in an antipsychotic-naive first episode of psychosis cohort. TRANSLATIONAL PSYCHIATRY, v. 8, AUG 31 2018. (14/50830-2, 14/07280-1, 14/22223-4, 12/12686-1, 10/08968-6, 16/13737-0, 16/04983-7, 11/50740-5)

SATO, JOAO RICARDO; BIAZOLI, CLAUDINEI EDUARDO; BUENO, ANA PAULA ARANTES; CAYE, ARTHUR; PAN, PEDRO MARIO; SANTORO, MARCOS; HONORATO-MAUER, JESSICA; SALUM, GIOVANNI ABRAHAO; HOEXTER, MARCELO QUEIROZ; BRESSAN, RODRIGO AFFONSECA; et al. Polygenic risk score for attention-deficit/hyperactivity disorder and brain functional networks segregation in a community-based sample. GENES BRAIN AND BEHAVIOR, v. N/A, p. 9-pg., 2023-02-21. (18/04654-9, 16/13737-0, 13/08531-5, 21/05332-8, 16/04983-7, 18/21934-5)