TS-EUROTRAIN - Projects

Integrated genetic networks underlying comorbid TS and OCD (WP2)

Objectives: 1. Detect and integrate common genetic pathways and genetic networks for neurodevelopmental disorders that are genetically related to TS (i.e. OCD and ADHD). 2. Identify common pleiotropic genetic risk variants as possible druggable targets.

Fellow ESR5   
Host institution: RUNMC
Duration
: 36 months    
Supervisor: J. Glennon, J. Buitelaar, RUNMC; Co-supervisor: P. Paschou (DUTH); Associated partner: J. Scharf, MGH; DI Boomsma, VU. Seconding Company: SENSA

Tasks and methodology: Common pleiotropic mechanisms may underlie shared repetitive symptoms across TS and OCD. We will determine the extent of ‘genetic overlap’ in terms of shared underlying gene pathways and gene networks between TS and OCD, to provide further insights into how aberrant processes underlie these genetically related, clinically overlapping but still distinct neurodevelopmental disorders. We have previously demonstrated this in genetic networks for ASD, dyslexia and ADHD. Using a combination of bioinformatics and literature approaches on top candidate genes from four GWASs of TS and two GWASs of OCD and corroborating genetic evidence including data from recurrent and ‘genome-wide’ CNV studies, microRNA data, animal models and gene expression studies; integrated genetic networks for the overlapping traits between TS and OCD will be constructed. The GWAS data will be provided by Dr. J. Scharf (Associated partner MGH), Dr. P. Paschou and Dr. P. Hoekstra (EU FP7 EMTICS consortium), Dr. DI Boomsma, (Dutch Twin Register) and deCODE Genetics.

  • Task 1: Evaluation of top candidate genes using bioinformatics approaches including Ingenuity analysis from the four GWASs of TS and two GWASs of OCD.
  • Task 2: Evaluation of top candidate genes for TS and OCD using literature searches corroborated by genetic evidence including data from recurrent and ‘genome-wide’ CNV studies, microRNA data, animal models and gene expression studies.
  • Task 3: Ranking of top candidate genes demonstrating overlap between TS and OCD.
  • Task 4: Construction of integrated gene networks for overlapping traits between TS and OCD.

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