Developing Clinical subtypes for Genetic Studies of Tourette Syndrome

Grant Type
Grant Year
Institution Location
Institution Organization Name
University of California
Investigators Name
Mathews, Carol, MD

This proposal aims to identify potential clinical subtypes within Tourette Syndrome (TS) and to use these to further inform genetic studies. This goal will be accomplished by using the extensive clinical information collected from more than 350 TS families as a part of the TSA International Consortium for Genetics (TSAICG) initiative. We will complete the diagnostic best-estimate assessments on these families and identify additional psychiatric diagnoses, such as mood or anxiety disorders, in the sibling pairs with TS. The completed clinical data, along with data on obsessive- compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) can then be used to a) examine the rates of neuropsychiatric disorders among families with TS and b) develop potential TS subtypes and related measures for genetic analysis. Existing genetic information from the recently completed whole genome screen and follow-up studies will be combined with the clinical data for the analyses proposed here. Two types of genetic analyses will be conducted. The first will use the presence or absence of highly associated comorbid psychiatric disorders including OCD, ADHD, anxiety disorders, major depression (MDD), and bipolar disorder (BPD), as covariates to further inform genetic analyses of TS. The second analysis will use data reduction techniques to derive classes or clusters of individuals with TS and comorbid psychiatric disorders using approaches such as factor analysis and latent class analysis (LCA). Affected classes can be used to test for within-family sameness (family specificity) and may be informative about other modes of genetic transmission. Factor or similarity scores generated can be used as continuous measures in quantitative trait locus (QTL) analyses, thereby increasing the power of the genetic studies. Carol Mathews, M.D., University of California-San Diego, San Diego, California Marco A. Grados, M.D., M.P.H., Johns Hopkins University School of Medicine, Baltimore, Maryland Award: $75,000 Tourette Association of America Inc. – Research Grant Award 2005-2006