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Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders. Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders.

A total population of 4,479 children (7-15 years of age) attended school in Ludvika & Smedjebacken in 2000. All the school children and their parents were asked to fill in a questionnaire concerning different tics A three-stage procedure was used: tic identification, interview, and clinical assessment. Tourette syndrome, according to DSM IV criteria was found in 25 (0.6%) of the children, another 34 (0.8%) suffered from chronic motor tics (CMT), 24 (0.4%) from chronic vocal tics (CVT) and 214 (4.8%) children had had transient tics (TT) during the last year. Altogether 297 (6.6%) children had or had had some tic disorder. Twenty-five controls without tics and 25 children with TT of the same age, sex and school as the TS children were randomly chosen. They were together with the 34 children with CMT and the 24 children with CVT examined with use of a broad battery of instruments. The mean age of the first symptoms of TS was significantly lower than the onset of chronic motor/vocal tics. A younger age of onset of TS indicated more severe tics. Eighty per cent had a first-degree relative with a psychiatric disorder such as tic disorder, obsessive-compulsive behaviour, attentiondeficit/hyperactivity disorder (ADHD), or depression. A non-significant increase with regard to reduced optimality score in the pre-, peri-, or neonatal periods was found in children with TS compared to controls. No differences were found concerning socio-economic status. Psychiatric comorbid disorders were found in 92% of the children with TS. ADHD was most common. Patterns of psychiatric comorbidity were similar in children with TS and CVT. Children with TS perform poorer than the population in general with respect to cognitive functioning and self-perception. The results are discussed as they relate to the need for case identification, diagnosis, intervention, and treatment.