Poster #102 - Subramanian Krishnamurthy¹

Biomarker Discovery in Tourette's Disorder

Subramanian Krishnamurthy¹,², Jay A. Tischfield¹,², Gary A. Heiman¹,², Jinchuan Xing¹,² ¹Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA ²Human Genome Institute of New Jersey, Rutgers, The State University of New Jersey

Tourette's disorder (TD) is a childhood onset neuro-developmental disorder (NDD), Characterized by Motor and Vocal tics. It has a large genetic component. A variety of DNA-based methods have been applied to identify genetic markers of TD, but the connection to RNA-based gene expression has not been fully exploited, though it has been used in other neuro developmental and neuro degenerative disorders. We used a cohort of cases (n=21) with TD and controls (n=21) without TD from the Tourette's International Collaborative Genetics Study (TICGenetics). One subject was selected from each family and subjects on medications with potentially confounding effect were excluded. This study utilized bulk RNA sequencing to identify expressed changes in whole blood RNA in TD. Multiple analytical strategies were employed to narrow differentially expressed RNA targets to a small set of potential biomarkers of TD. We identified 19 genes that had statistically significant fold change > 2. 11 were up-regulated and 8 were down regulated. Ten of the genes are known to be associated with brain development and neurological disorders. For example, NRCAM (Neuronal Cell Adhesion Molecule) is known to be associated with neuro development disorders, LRRN3 (Leucine Rich Repeat Neuronal 3) with Autism, CCR8 (C-C Motif Chemokine Receptor 8) with Multiple Sclerosis and 7 others with Epilepsy / Schizophrenia. Data from this preliminary study suggests these may be promising targets for diagnostics and therapeutics in TD.