TY - JOUR
T1 - Latent Class Analysis of Gilles de la Tourette Syndrome Using Comorbidities
T2 - Clinical and Genetic Implications
AU - Grados, Marco A.
AU - Mathews, Carol A.
N1 - Funding Information:
The TSAICG acknowledges J. Hebebrand, B. Klug, and H. Remschmidt, Department of Child and Adolescent Psychiatry, Phipps University, Marburg Germany; J.L. Weber, B.C. Hiner, and M. Spindler, Center for Medical Genetics, Marshfield Medical Foundation, Marshfield, WI; and J. Jancovic, Department of Neurology, Baylor College of Medicine, Houston, TX, for their assistance in collecting data from sib-pair families that were included in this genome scan. This work was supported by funds from the TSA and from National Institutes of Health Grant No. NS 40024.
PY - 2008/8/1
Y1 - 2008/8/1
N2 - Background: 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. Methods: 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. Results: 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. Conclusions: 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.
AB - Background: 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. Methods: 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. Results: 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. Conclusions: 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.
KW - Attention-deficit/hyperactivity disorder
KW - Tourette syndrome
KW - genetics
KW - obsessive-compulsive disorder
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U2 - 10.1016/j.biopsych.2008.01.019
DO - 10.1016/j.biopsych.2008.01.019
M3 - Article
C2 - 18359008
AN - SCOPUS:46249102042
SN - 0006-3223
VL - 64
SP - 219
EP - 225
JO - Biological psychiatry
JF - Biological psychiatry
IS - 3
ER -