title: Tic symptom dimensions and their heritabilities in Tourette's syndrome.
abstract: BACKGROUND
  Gilles de la Tourette's syndrome (TS) is both genotypically and phenotypically heterogeneous. Gene-finding strategies have had limited success, possibly because of symptom heterogeneity.
  
  
  OBJECTIVE
  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 USA (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 carried out on 23 tic symptoms from the Yale Global Tic Severity Scale.
  
  
  RESULTS
  Three factors were identified explaining 49% of the total variance: factor 1, complex vocal tics and obscene behaviour; factor 2, body tics; and factor 3, head/neck tics. Using Sequential Oligogenic Linkage Analysis Routine, moderate heritabilities were found for factor 1 (h2r=0.21) and factor 3 (h2r=0.25). Lower heritability was found for overall tic severity (h2r=0.19). Bivariate analyses indicated no genetic associations between tic factors.
  
  
  CONCLUSIONS
  These findings suggest that (i) three tic factors can be discerned with a distinct underlying genetic architecture and that (ii) considering the low tic heritabilities found, only focusing 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.
authors.affiliation: aInstitut de Neurosciences de la Timone INT, Marseille, France bInstitute of Neuroscience INM-6, Research Center Jülich, Jülich, Germany cDepartment of Psychiatry, VU University Medical Centre VUmc, Amsterdam dDepartment of Clinical & Health Psychology, Utrecht University eAltrecht Academic Anxiety Center, Utrecht, The Netherlands fPsychiatry, Epidemiology & Biostatistics gDepartment of Psychiatry, University of California, San Francisco, USA.
authors.forename: Marcel J
authors.initials: MJ
authors.lastname: de Haan
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Delucchi
authors.forename: Carol M
authors.initials: CM
authors.lastname: Mathews
authors.forename: Danielle C
authors.initials: DC
authors.lastname: Cath
mesh_terms: D000293:Adolescent; D000328:Adult; D003364:Costa Rica; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D011569:Psychiatric Status Rating Scales; D020323:Tics / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D005879:Tourette Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D014481:United States; D055815:Young Adult