Integrative Genetic Approaches to Rare Variant Discovery in Co-morbid OCD and Tic Disorder

Grant Type
Grant Year
Institution Location
Institution Organization Name
University of California
Investigators Name
Nurmi, Erika L., MD, PhD

In some families, co-associated Obsessive-Compulsive Disorder (OCD) and Tic Disorder (OCD+tics) are passed on from one generation to the next over many generations. While still novel, next generation sequencing (NGS) technology has been successful at molecular diagnosis and mapping of numerous Mendelian disorders including several within our laboratory. In our extensively phenotyped OCD Collaborative Genetics Study (OCGS) we have identified a number of women who have the OCD+tics phenotype. Using genetic techniques such as identity by descent (IBD), homozygosity,and copy number variant (CNV) mapping, we have identified regions of DNA and candidate genes for the OCD+tic phenotype. In this study we plan to employ NGS technology to identify risk alleles within these intervals. Due to relatively strong genetic effects, the OCD+tic phenotype is an ideal candidate for exploring the application of promising genetic technologies to complex neuropsychiatric disease. A deeper understanding of the genetic risk for co-morbid OCD and Tic Disorder will help define the brain circuits involved and yield targets for the design of new therapeutic agents. The discovery of risk alleles for these conditions promises to improve diagnosis and predict prognosis for affected individuals and may lead to the personalization of effective treatments based on molecular diagnosis. Ultimately, identification of those at risk could enable early intervention and perhaps prevention. Erika L. Nurmi, M.D., Ph.D., Stanley F. Nelson, M.D., James T. McCracken, M.D. University of California, Los Angeles, CA Award: $71,843 Commentary: The investigators will utilize merging and powerful DNA analysis technologies to find risk genes in people with both Obsessive Compulsive Disorder (OCD) and Tic Disorder. By analyzing DNA from affected families they have already identified regions of the DNA likely to harbor such genes. By determining the complete DNA sequence within these regions in select families they will be able to identify DNA changes that confer risk for developing OCD and tics. Their results could broaden our understanding, improve diagnosis, predict prognosis and guide novel drug design for people with OCD and tics. Ultimately, they may allow for the personalization of treatment and early intervention with the hope of prevention. Tourette Association of America Inc. – Research Grant Award 2011-2012