M70 DETERMINING THE GENETIC OVERLAP BETWEEN TOURETTE SYNDROME (TS) OBSESSIVE COMPULSIVE DISORDER (OCD) AND OCD/TIC RELATED TRAITS
Venue: European Neuropsychopharmacology
Year: 2019

Tourette Syndrome (TS) and Obsessive Compulsive Disorder (OCD) are heritable neuropsychiatric disorders with a childhood onset. TS is characterized by multiple and involuntary motor tics and at least one vocal tic that persists for more than one year. TS has a prevalence of 0,3 0,8% OCD is characterized by recurring obsessions and/or compulsions and affects up to 2% of the population. The disorders often co occur, with their comorbidity ranging between 20 60% Moreover, there are striking similarities in the phenotypic representation of TS/tics and OCD. Previous studies indicate that TS and OCD may share some common genetic susceptibility factors with an estimated genetic correlation of 0.41 but also suggest that there are distinct components to the genetic architectures of the two disorders. Two recent population based twin sample studies also reported genetic correlations between tics and OCD related traits (0.37 and 0.45) In this study we further investigated the shared genetic etiology between TS, OCD, and OCD traits as well as tic traits in the general population.  We conducted a number of Polygenic Risk Score (PRS) based analyses. For these analyses, we used the summary statistics data from the Genome Wide Association Study (GWAS) of TS and the summary statistics from the meta analysis of the two GWASs of OCD conducted by the Psychiatric Genomics Consortium (PGC) (unpublished, provided by PGC OCD Working Group) as the 'base' sample. As 'target' samples, we used summary statistics of GWASs of OCD traits and tic traits in the general population. For these GWASs, we used phenotypic and genotyping data from the Children's Hospital of Philadelphia (CHOP) cohort obtained from dbGaP (phs000607.v1.p1) To conduct the OCD trait GWASs, we first developed a questionnaire consisting of 22 OCD trait questions and conducted a factor analysis of the questionnaire, to reveal the subsets of OCD traits that group together and may better capture the underlying genetic architecture. We then conducted GWASs of the total score on the 22 OCD trait questions and of six OCD trait factors in 650 children and adolescents from the CHOP cohort. For tic traits, we conducted a GWAS on the total score on 4 tic trait questions in 207 individuals from the CHOP cohort.  The factor analysis of the 22 OCD trait questions revealed 8 factors that constitute the best fit and explain 58,6% of the variance in the total score on the 22 questions, i.e. 'impairment' 'symmetry/counting/ordering' 'contamination/cleaning' 'aggressive taboo thoughts (tt) 'repetition' 'guilty tt' 'distress' and 'religious tt' The PRS based analyses yielded a significant evidence for shared genetic etiology between OCD and the three OCD traits 'impairment' (1.06% variance explained (ve) 'contamination/cleaning' (3.54% ve, and 'guilty taboo thoughts' (5.64% ve) Furthermore, we found significant shared genetic etiology between TS and four OCD traits: 'symmetry/counting/ordering' (3.03% ve) 'contamination/cleaning' (1.28% ve) 'aggressive taboo thoughts' (4.96% ve) and 'distress' (1.83% ve) and between TS and the total score on tic traits (4.78% ve) OCD and TS did not show significant genetic overlap with the total score on the 22 OCD trait questions.  Our findings provide additional and novel evidence that certain OCD traits show genetic overlap with OCD and TS, which adds to our understanding of the genetic risk factors that are shared by and unique to these comorbid disorders.