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Integrated investigation of gene expression and DNA metilation in obsessive-compulsive disorder

Grant number: 20/12484-6
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): January 01, 2021
Effective date (End): December 31, 2025
Field of knowledge:Health Sciences - Medicine - Psychiatry
Principal Investigator:Eurípedes Constantino Miguel Filho
Grantee:Leonardo Cardoso Saraiva
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:14/50917-0 - INCT 2014: developmental psychiatry for children and adolescents, AP.TEM
Associated scholarship(s):22/10207-0 - Imaging transcriptomics in obsessive-compulsive disorder, BE.EP.DD

Abstract

Obsessive-Compulsive Disorder (OCD) is associated with elevated prevalence and morbidity, however first-line treatments benefit satisfactorily only half of the patients with the disorder. The elucidation of the biological basis of OCD can contribute to the development of more efficient approaches for diagnosis and treatment. In line with the genetic nature of OCD, initial investigations demonstrated that dysregulations in gene expression and DNA methylation are involved in the biologic mechanisms underlying the disorder. Nonetheless, previous studies ofgene expression and DNA methylation in OCD have methodologic and technologic limitations. First, no study has performed the integrated investigation of gene expression and DNA methylation, which allows for the evaluationof their interactions in biological pathways involved in OCD. Furthermore, no study has included first-degree relatives of patients with OCD, which allows for the investigation of alterations in gene expression and DNA methylation associated with the risk of developing the disorder. Finally, there are more accurate technologies for the measurement of gene expression and DNA methylation than those used previously. As such, the aim of this project is to conduct an integrated investigation of gene expression and DNA methylation in peripheral blood samples of 150 patients with OCD, 150 of their first-degree relatives and 150 healthy individuals. The methodologic state of the art for measurement of gene expression and DNA methylation will be used. The hypothesis of this project is that it will be identified gene differentially expressed and genomic regions differentially methylated between the groups and that these genes and regions will be connected in co-expression and co-methylation networks, respectively. Therefore, it will be possible to detect alterations in gene expression and DNA methylation associated with OCD and with risk of developing OCD, in addition to the biological pathways involved in those alterations. (AU)

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