Archival Report| Volume 64, ISSUE 3, P219-225, August 01, 2008

Latent Class Analysis of Gilles de la Tourette Syndrome Using Comorbidities: Clinical and Genetic Implications

  • Marco A. Grados
    Address reprint requests to Marco A. Grados, M.D., M.P.H., Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, 600 North Wolfe St., CMSC 346, Baltimore, MD 21287.
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland
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  • Carol A. Mathews
    Department of Psychiatry, University of California, San Francisco.
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  • Tourette Syndrome Association International Consortium for Genetics


      Although susceptibility loci exist for Gilles de la Tourette syndrome (GTS), no causative gene has been identified, perhaps in part because of phenotypic heterogeneity. This study used latent class analyses (LCA) to identify GTS subphenotypes and assess characteristics and heritability of the classes.


      The study included 952 individuals from 222 GTS families recruited for genetic studies. LCA identified a best-fit model for combinations of the diagnoses of GTS, obsessive-compulsive disorder (OCD), OC symptoms and behaviors (OCS/OCB), and attention-deficit/hyperactivity disorder (ADHD) in a random sample of one sibling from each family (n = 197), a replication sample randomly chosen from the remaining siblings (n = 203), and in the entire sample (all siblings and parents, N = 952). Heritabilities were assessed for all categoric diagnoses and LCA classes using a variance components approach.


      In this large sample of GTS sib pairs and their parents, three GTS-affected groups were identified—GTS + OCS/OCB (Class III), GTS + OCD (Class IV), and GTS + OCD + ADHD (Class V)—in addition to a minimally affected class (I) and a small chronic tics + OCD class (II). A preponderance of males and younger age at onset was found in more comorbidly affected classes. Only the GTS + OCD + ADHD class was highly heritable.


      Our data suggest that GTS classes may represent distinct entities, with both shared and unique etiologies. In particular, GTS + OCD + ADHD may represent a separate, heritable phenotype that can be used to further inform genetic studies.

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