Elsevier

Biological Psychiatry

Volume 64, Issue 3, 1 August 2008, Pages 219-225
Biological Psychiatry

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

https://doi.org/10.1016/j.biopsych.2008.01.019Get rights and content

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.

Section snippets

Sample

The sample consisted of 952 individuals from 222 GTS families collected by the Tourette Syndrome Association International Consortium on Genetics (TSAICG) for affected sibling pair (ASP) genetic linkage studies (18, 19). Families were ascertained on the basis of presence of GTS in at least two siblings and the availability of at least one parent. Families were excluded if the proband had mental retardation or a pervasive developmental disorder or where both parents had a known diagnosis of GTS,

Sample Characteristics

From this sib-pair GTS sample, most affecteds (n = 668) had GTS diagnoses (n = 596), and a minority had CT diagnoses (n = 72). Subjects with GTS had a younger age at onset of tics and more frequent comorbid OCD and ADHD diagnoses compared with subjects with CT (Table 1).

Considering only GTS subjects, 75% had either OCD or ADHD, with approximately a third of the sample having both OCD and ADHD. The other third had comorbid OCD only, and a smaller subset (10%) had comorbid ADHD only (Figure 1).

Latent Class Analyses

Discussion

This study represents the first latent class analysis of GTS and its most common comorbidities, OCD and ADHD. We identified three GTS-affected classes, corresponding to GTS + OCS/OCB (Class III; n = 107), GTS + OCD (Class IV; n = 300), and GTS + OCD + ADHD (Class V; n = 229). Two additional classes were also identified in the larger family sample: minimal disorder (Class I; n = 281) and chronic tics (Class II; n = 35). We are confident that the LCA classes derived from these analyses are

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