Tic symptom dimensions and their heritabilities in Tourette’s syndrome

Abstract

Gilles de la Tourette’s syndrome (TS) is both genotypically and phenotypically heterogeneous. Gene finding strategies have had limited success, possibly due to symptom heterogeneity. Objectives This study aimed at specifically investigating heritabilities of tic symptom factors in a relatively large sample of TS patients and family members. Methods Lifetime tic symptom data were collected in 494 diagnosed individuals, in two cohorts of TS patients from the US (n=273) and the Netherlands (n=221), and in 351 Dutch family members. Item-level factor analysis, using a tetrachoric correlation matrix in SAS (v9.2), was conducted on 23 tic symptoms from the Yale Global Tic Severity Scale (YGTSS). Results Three factors were identified explaining 49% of the total variance: factor 1) complex vocal tics & obscene behaviour; factor 2) body tics; and factor 3) head/neck tics. Using Sequential Oligogenic Linkage Analysis Routine (SOLAR) moderate heritabilities were found for factor 1 (h2 = 0.21) and factor 3 (h2 = 0.25). Lower heritability was found for overall tic severity (h2 = 0.19). Bi-variate analyses revealed no genetic associations between tic factors. Conclusions Thus, these findings suggest that 1) three tic factors can be discerned with a distinct underlying genetic architecture, and that 2) considering the low tic heritabilities found, only focussing on the narrow-sense TS phenotype and leaving out comorbidities that are part of the broader sense tic phenotype, may lead to missing heritability. Although these findings need replication in larger independent samples, they might have consequences for future genetic studies in TS.

The relationship between tics, OC, ADHD and autism symptoms: A cross- disorder symptom analysis in Gilles de la Tourette syndrome patients and family-members

“…The current study samples partially overlap with the study samples described in de Haan et al (2015). More specifically, the family sample of the de Haan et al study is similar to the family sample in this study, whereas the patient sample of the de Haan et al (2015) study has included n=183 Dutch patients that are also included in the current study. The current patient sample included an additional 42 subjects.…”

“…All analyses were first run in the GTS sample and then in the family Sample, to cross-validate the results, and to investigate generalizability of the results from the GTS patient sample to a sample of largely unaffected family members. One of the models we tested was derived from a study of de Haan (2015), who used the same sample as the replication sample used in our study. However because our findings were tested in two different samples this is not a problem for the results of our study.…”

“…Depending on sample size, analytic method used, and definitions of the symptoms/symptom categories under investigation (e.g., broad versus strict), varying numbers of symptom dimensions have been found across studies. In short, with respect to tic symptoms as measured with the widely used Yale Global Tic Severity Scale (YGTSS) (Leckman et al, 1989), between 2 and 5 factors were found (Alsobrook and Pauls, 2002; Mathews et al, 2007; Robertson et al, 2008; de Haan et al, 2015), on the Yale-Brown Obsessive Compulsive Symptom Scale (YBOCS) (Goodman et al, 1989), between 3 and 5 factors were found (Baer et al, 1994; McKay et al, 1995; Leckman et al, 1997; Katerberg et al, 2010), on the Connors Attention Deficit & Hyperactivity Rating Scale (CAARS) (Conners et al, 1999) 2–3 factors (Conners et al., 1999; Hardy et al, 2007), and finally on the Autism spectrum Quotient (AQ) (Baron-Cohen et al, 2001) 5 factors have been identified, although content of the symptom dimensions somewhat changed with re-analysis and abbreviation of the scale (Baron-Cohen et al, 2001; Hoekstra et al, 2011). …”

Tourette syndrome research highlights from 2016

“…Sambrani et al 13 felt that their data supported lumping SIB with coprophenomena, and argue for it to “be conceptualized as a complex tic rather than a compulsion.” Others have found similar results 19 , though other results support a connection to compulsions 20 , one large study found SIB to fit better with ADHD symptoms 21 , and another linked it to both OCD and ADHD 22 .…”

Epigenome-Wide Association Study of Tic Disorders

“…Future studies of larger size or including clinical samples at the more extreme end of the tic phenotypic spectrum are required to improve statistical power. Future studies should also aim to examine different phenotypic tic dimensions (de Haan et al, 2015). Such studies hold the promise to shed light on the complex interaction between environmental and genetic factors leading to development and persistence of neuropsychiatric disorders.…”