TY - JOUR
T1 - Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome
AU - The EMTICS collaborative group
AU - The Psychiatric Genomics Consortium Tourette Syndrome Working Group (PGC-TS)
AU - The TS-EUROTRAIN Network
AU - Jain, Pritesh
AU - Miller-Fleming, Tyne
AU - Topaloudi, Apostolia
AU - Yu, Dongmei
AU - Drineas, Petros
AU - Georgitsi, Marianthi
AU - Yang, Zhiyu
AU - Rizzo, Renata
AU - Müller-Vahl, Kirsten R.
AU - Tumer, Zeynep
AU - Mol Debes, Nanette
AU - Hartmann, Andreas
AU - Depienne, Christel
AU - Worbe, Yulia
AU - Mir, Pablo
AU - Cath, Danielle C.
AU - Boomsma, Dorret I.
AU - Roessner, Veit
AU - Wolanczyk, Tomasz
AU - Janik, Piotr
AU - Szejko, Natalia
AU - Zekanowski, Cezary
AU - Barta, Csaba
AU - Nemoda, Zsofia
AU - Tarnok, Zsanett
AU - Buxbaum, Joseph D.
AU - Grice, Dorothy
AU - Glennon, Jeffrey
AU - Stefansson, Hreinn
AU - Hengerer, Bastian
AU - Benaroya-Milshtein, Noa
AU - Cardona, Francesco
AU - Hedderly, Tammy
AU - Heyman, Isobel
AU - Huyser, Chaim
AU - Morer, Astrid
AU - Mueller, Norbert
AU - Munchau, Alexander
AU - Plessen, Kerstin J.
AU - Porcelli, Cesare
AU - Walitza, Susanne
AU - Schrag, Anette
AU - Martino, Davide
AU - Als, Thomas D.
AU - Aschauer, Harald
AU - Atzmon, Gil
AU - Bækvad-Hansen, Matie
AU - Barr, Cathy L.
AU - Barzilai, Nir
AU - Batterson, James R.
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41398-023-02341-5
DO - 10.1038/s41398-023-02341-5
M3 - Article
C2 - 36823209
AN - SCOPUS:85148805353
SN - 2158-3188
VL - 13
JO - Translational psychiatry
JF - Translational psychiatry
IS - 1
M1 - 69
ER -
