Key result
Higher Tourette syndrome polygenic risk score was significantly associated with 57 phenotypes, most strongly with having seen a doctor for nerves, anxiety, or depression (beta 0.031, p=9.2x10^-17).
Why the study?
Although Tourette Syndrome correlates with other phenotypes epidemiologically, large-scale phenome-wide analyses in biobank-level data had not been performed.
Observational (n=330,841)
Effect estimate: beta: 0.031
p-value: p=9.2 x 10^-17
Higher polygenic risk for Tourette syndrome is significantly associated with multiple psychosocial factors, mental health conditions, and complex non-psychiatric disorders like type 2 diabetes and heart palpitations.
Hypothesis-generating for TS polygenic pleiotropy with mental health and cardiometabolic traits; prospective studies required before clinical use.
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.
No takes yet. Share an insight, caveat, or question.
Jain et al. (2023) conducted an observational in Tourette Syndrome genetic risk (n=330,841). Tourette syndrome polygenic risk score (PRS) vs. Lower polygenic risk score was evaluated on Phenome-wide associations with TS PRS (strongest association: Seen doctor for nerves, anxiety or depression) (beta: 0.031, p=9.2 x 10^-17). Higher Tourette syndrome polygenic risk score was significantly associated with 57 phenotypes, most strongly with having seen a doctor for nerves, anxiety, or depression (beta 0.031, p=9.2x10^-17).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: