De novo and rare inherited variants in obsessive-compulsive disorder

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)