De novo and rare inherited variants in obsessive-compulsive disorder

• Grant number: 14/01585-5
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): May 01, 2014
• Effective date (End): January 27, 2020
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal researcher: Eurípedes Constantino Miguel Filho
• Grantee: Carolina Cappi
• Home 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): 17/26183-5 - Next Generation Sequencing in multiplex OCD families and ASD families, BE.EP.PD

Abstract

The main objective of this project is to investigate the involvement of genome de novo and inherited rare variations in a sample of patients with Obsessive-compulsive disorder (OCD) (n=80) and their family members (n=80 families) using whole exome sequencing. Based on the observation that genes associated with similar diseases are likely to interact with each other heavily in a network, we will generate a protein-protein network with the genes with rare variations. To investigate the relevance of this network to OCD, we will apply an algorithm to rank all genes with rare variation based on their relatedness to a set of candidate genes previously identified in OCD. In addition, pathway analyses using genes with rare variations will be performed. Simultaneously, rare variations frequency will be correlated to performance in behavior paradigms of fear and anxiety that are relevant to OCD. Finally, these findings involving rare variation obtained in peripheral DNA will be validated in biological material (cells of brain tissue) from OCD patients submitted to deep brain stimulation. (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)

CAPPI, CAROLINA; OLIPHANT, MELODY E.; PETER, ZSANETT; ZAI, GWYNETH; DO ROSARIO, MARIA CONCEICAO; SULLIVAN, CATHERINE A. W.; GUPTA, ABHA R.; HOFFMAN, ELLEN J.; VIRDEE, MANMEET; OLFSON, EMILY; ABDALLAH, SARAH B.; WILLSEY, A. JEREMY; SHAVITT, ROSELI G.; MIGUEL, EURIPEDES C.; KENNEDY, JAMES L.; RICHTER, MARGARET A.; FERNANDEZ, THOMAS V. De Novo Damaging DNA Coding Mutations Are Associated With Obsessive-Compulsive Disorder and Overlap With Tourette's Disorder and Autism. BIOLOGICAL PSYCHIATRY, v. 87, n. 12, p. 1035-1044, JUN 15 2020. Web of Science Citations: 1.

GONCALVES, VANESSA F.; CAPPI, CAROLINA; HAGEN, CHRISTIAN M.; SEQUEIRA, ADOLFO; VAWTER, MARQUIS P.; DERKACH, ANDRIY; ZAI, CLEMENT C.; HEDLEY, PAULA L.; BYBJERG-GRAUHOLM, JONAS; POUGET, JENNIE G.; CUPERFAIN, ARI B.; SULLIVAN, PATRICK F.; CHRISTIANSEN, MICHAEL; KENNEDY, JAMES L.; SUN, LEI. A Comprehensive Analysis of Nuclear-Encoded Mitochondrial Genes in Schizophrenia. BIOLOGICAL PSYCHIATRY, v. 83, n. 9, p. 780-789, MAY 1 2018. Web of Science Citations: 3.

CAPPI, CAROLINA; DINIZ, JULIANA BELO; REQUENA, GUARACI L.; LOURENCO, TIAYA; GARCIA LISBOA, BIANCA CRISTINA; BATISTUZZO, MARCELO CAMARGO; MARQUES, ANDREA H.; HOEXTER, MARCELO Q.; PEREIRA, CARLOS A.; MIGUEL, EURIPEDES CONSTANTINO; BRENTANI, HELENA. Epigenetic evidence for involvement of the oxytocin receptor gene in obsessive-compulsive disorder. BMC NEUROSCIENCE, v. 17, NOV 30 2016. Web of Science Citations: 14.