Genome-wide Association Study points to novel locus for Gilles de la Tourette Syndrome

Fotis Tsetsos; Apostolia Topaloudi; Pritesh Jain; Zhiyu Yang; Dongmei Yu; Petros Kolovos; Zeynep Tumer; Renata Rizzo; Andreas Hartmann; Christel Depienne; Yulia Worbe; Kirsten R Müller-Vahl; Danielle C Cath; Dorret I Boomsma; Tomasz Wolanczyk; Cezary Zekanowski; Csaba Barta; Zsofia Nemoda; Zsanett Tarnok; Shanmukha S Padmanabhuni; Joseph D Buxbaum; Dorothy Grice; Jeffrey Glennon; Hreinn Stefansson; Bastian Hengerer; Evangelia Yannaki; John A Stamatoyannopoulos; Noa Benaroya-Milshtein; Francesco Cardona; Tammy Hedderly; Isobel Heyman; Chaim Huyser; Pablo Mir; Astrid Morer; Norbert Mueller; Alexander Munchau; Kerstin J Plessen; Cesare Porcelli; Veit Roessner; Susanne Walitza; Anette Schrag; Davide Martino; Jay A Tischfield; Gary A Heiman; A Jeremy Willsey; Andrea Dietrich; Lea K Davis; James J Crowley; Carol A Mathews; Jeremiah M Scharf; PGC TS Working Group

doi:10.1016/j.biopsych.2023.01.023

Genome-wide Association Study points to novel locus for Gilles de la Tourette Syndrome

Fotis Tsetsos, Apostolia Topaloudi, Pritesh Jain, Zhiyu Yang, Dongmei Yu, Petros Kolovos, Zeynep Tumer, Renata Rizzo, Andreas Hartmann, Christel Depienne, Yulia Worbe, Kirsten R Müller-Vahl, Danielle C Cath, Dorret I Boomsma, Tomasz Wolanczyk, Cezary Zekanowski, Csaba Barta, Zsofia Nemoda, Zsanett Tarnok, Shanmukha S PadmanabhuniJoseph D Buxbaum, Dorothy Grice, Jeffrey Glennon, Hreinn Stefansson, Bastian Hengerer, Evangelia Yannaki, John A Stamatoyannopoulos, Noa Benaroya-Milshtein, Francesco Cardona, Tammy Hedderly, Isobel Heyman, Chaim Huyser, Pablo Mir, Astrid Morer, Norbert Mueller, Alexander Munchau, Kerstin J Plessen, Cesare Porcelli, Veit Roessner, Susanne Walitza, Anette Schrag, Davide Martino, Jay A Tischfield, Gary A Heiman, A Jeremy Willsey, Andrea Dietrich, Lea K Davis, James J Crowley, Carol A Mathews, Jeremiah M Scharf^*, PGC TS Working Group

^*Corresponding author af dette arbejde

10 Citationer (Scopus)

Abstract

BACKGROUND: Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture and is characterized by multiple motor tics and at least one vocal tic persisting for more than 1 year.

METHODS: We performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6133 individuals with TS and 13,565 ancestry-matched control participants.

RESULTS: We identified a genome-wide significant locus on chromosome 5q15. Integration of expression quantitative trait locus, Hi-C (high-throughput chromosome conformation capture), and genome-wide association study data implicated the NR2F1 gene and associated long noncoding RNAs within the 5q15 locus. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring of brain volume data identified statistically significant associations with right and left thalamus volumes and right putamen volume.

CONCLUSIONS: Our work presents novel insights into the neurobiology of TS, thereby opening up new directions for future studies.

Originalsprog	Engelsk
Tidsskrift	Biological Psychiatry
Vol/bind	96
Udgave nummer	2
Sider (fra-til)	114-124
Antal sider	11
ISSN	0006-3223
DOI	https://doi.org/10.1016/j.biopsych.2023.01.023
Status	Udgivet - 15 jul. 2024

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Tsetsos, F., Topaloudi, A., Jain, P., Yang, Z., Yu, D., Kolovos, P., Tumer, Z., Rizzo, R., Hartmann, A., Depienne, C., Worbe, Y., Müller-Vahl, K. R., Cath, D. C., Boomsma, D. I., Wolanczyk, T., Zekanowski, C., Barta, C., Nemoda, Z., Tarnok, Z., ... PGC TS Working Group (2024). Genome-wide Association Study points to novel locus for Gilles de la Tourette Syndrome. Biological Psychiatry, 96(2), 114-124. https://doi.org/10.1016/j.biopsych.2023.01.023

Tsetsos, F, Topaloudi, A, Jain, P, Yang, Z, Yu, D, Kolovos, P, Tumer, Z, Rizzo, R, Hartmann, A, Depienne, C, Worbe, Y, Müller-Vahl, KR, Cath, DC, Boomsma, DI, Wolanczyk, T, Zekanowski, C, Barta, C, Nemoda, Z, Tarnok, Z, Padmanabhuni, SS, Buxbaum, JD, Grice, D, Glennon, J, Stefansson, H, Hengerer, B, Yannaki, E, Stamatoyannopoulos, JA, Benaroya-Milshtein, N, Cardona, F, Hedderly, T, Heyman, I, Huyser, C, Mir, P, Morer, A, Mueller, N, Munchau, A, Plessen, KJ, Porcelli, C, Roessner, V, Walitza, S, Schrag, A, Martino, D, Tischfield, JA, Heiman, GA, Willsey, AJ, Dietrich, A, Davis, LK, Crowley, JJ, Mathews, CA, Scharf, JM & PGC TS Working Group 2024, 'Genome-wide Association Study points to novel locus for Gilles de la Tourette Syndrome', Biological Psychiatry, bind 96, nr. 2, s. 114-124. https://doi.org/10.1016/j.biopsych.2023.01.023

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title = "Genome-wide Association Study points to novel locus for Gilles de la Tourette Syndrome",

abstract = "BACKGROUND: Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture and is characterized by multiple motor tics and at least one vocal tic persisting for more than 1 year.METHODS: We performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6133 individuals with TS and 13,565 ancestry-matched control participants.RESULTS: We identified a genome-wide significant locus on chromosome 5q15. Integration of expression quantitative trait locus, Hi-C (high-throughput chromosome conformation capture), and genome-wide association study data implicated the NR2F1 gene and associated long noncoding RNAs within the 5q15 locus. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring of brain volume data identified statistically significant associations with right and left thalamus volumes and right putamen volume.CONCLUSIONS: Our work presents novel insights into the neurobiology of TS, thereby opening up new directions for future studies.",

keywords = "GWAS, Meta-analysis, NR2F1, Tourette syndrome",

author = "Fotis Tsetsos and Apostolia Topaloudi and Pritesh Jain and Zhiyu Yang and Dongmei Yu and Petros Kolovos and Zeynep Tumer and Renata Rizzo and Andreas Hartmann and Christel Depienne and Yulia Worbe and M{\"u}ller-Vahl, {Kirsten R} and Cath, {Danielle C} and Boomsma, {Dorret I} and Tomasz Wolanczyk and Cezary Zekanowski and Csaba Barta and Zsofia Nemoda and Zsanett Tarnok and Padmanabhuni, {Shanmukha S} and Buxbaum, {Joseph D} and Dorothy Grice and Jeffrey Glennon and Hreinn Stefansson and Bastian Hengerer and Evangelia Yannaki and Stamatoyannopoulos, {John A} and Noa Benaroya-Milshtein and Francesco Cardona and Tammy Hedderly and Isobel Heyman and Chaim Huyser and Pablo Mir and Astrid Morer and Norbert Mueller and Alexander Munchau and Plessen, {Kerstin J} and Cesare Porcelli and Veit Roessner and Susanne Walitza and Anette Schrag and Davide Martino and Tischfield, {Jay A} and Heiman, {Gary A} and Willsey, {A Jeremy} and Andrea Dietrich and Davis, {Lea K} and Crowley, {James J} and Mathews, {Carol A} and Scharf, {Jeremiah M} and {PGC TS Working Group}",

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T1 - Genome-wide Association Study points to novel locus for Gilles de la Tourette Syndrome

AU - Tsetsos, Fotis

AU - Topaloudi, Apostolia

AU - Jain, Pritesh

AU - Yang, Zhiyu

AU - Yu, Dongmei

AU - Kolovos, Petros

AU - Tumer, Zeynep

AU - Rizzo, Renata

AU - Hartmann, Andreas

AU - Depienne, Christel

AU - Worbe, Yulia

AU - Müller-Vahl, Kirsten R

AU - Cath, Danielle C

AU - Boomsma, Dorret I

AU - Wolanczyk, Tomasz

AU - Zekanowski, Cezary

AU - Barta, Csaba

AU - Nemoda, Zsofia

AU - Tarnok, Zsanett

AU - Padmanabhuni, Shanmukha S

AU - Buxbaum, Joseph D

AU - Grice, Dorothy

AU - Glennon, Jeffrey

AU - Stefansson, Hreinn

AU - Hengerer, Bastian

AU - Yannaki, Evangelia

AU - Stamatoyannopoulos, John A

AU - Benaroya-Milshtein, Noa

AU - Cardona, Francesco

AU - Hedderly, Tammy

AU - Heyman, Isobel

AU - Huyser, Chaim

AU - Mir, Pablo

AU - Morer, Astrid

AU - Mueller, Norbert

AU - Munchau, Alexander

AU - Plessen, Kerstin J

AU - Porcelli, Cesare

AU - Roessner, Veit

AU - Walitza, Susanne

AU - Schrag, Anette

AU - Martino, Davide

AU - Tischfield, Jay A

AU - Heiman, Gary A

AU - Willsey, A Jeremy

AU - Dietrich, Andrea

AU - Davis, Lea K

AU - Crowley, James J

AU - Mathews, Carol A

AU - Scharf, Jeremiah M

AU - PGC TS Working Group

PY - 2024/7/15

Y1 - 2024/7/15

N2 - BACKGROUND: Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture and is characterized by multiple motor tics and at least one vocal tic persisting for more than 1 year.METHODS: We performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6133 individuals with TS and 13,565 ancestry-matched control participants.RESULTS: We identified a genome-wide significant locus on chromosome 5q15. Integration of expression quantitative trait locus, Hi-C (high-throughput chromosome conformation capture), and genome-wide association study data implicated the NR2F1 gene and associated long noncoding RNAs within the 5q15 locus. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring of brain volume data identified statistically significant associations with right and left thalamus volumes and right putamen volume.CONCLUSIONS: Our work presents novel insights into the neurobiology of TS, thereby opening up new directions for future studies.

AB - BACKGROUND: Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture and is characterized by multiple motor tics and at least one vocal tic persisting for more than 1 year.METHODS: We performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6133 individuals with TS and 13,565 ancestry-matched control participants.RESULTS: We identified a genome-wide significant locus on chromosome 5q15. Integration of expression quantitative trait locus, Hi-C (high-throughput chromosome conformation capture), and genome-wide association study data implicated the NR2F1 gene and associated long noncoding RNAs within the 5q15 locus. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring of brain volume data identified statistically significant associations with right and left thalamus volumes and right putamen volume.CONCLUSIONS: Our work presents novel insights into the neurobiology of TS, thereby opening up new directions for future studies.

KW - GWAS

KW - Meta-analysis

KW - NR2F1

KW - Tourette syndrome

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U2 - 10.1016/j.biopsych.2023.01.023

DO - 10.1016/j.biopsych.2023.01.023

M3 - Journal article

C2 - 36738982

SN - 0006-3223

VL - 96

SP - 114

EP - 124

JO - Biological Psychiatry

JF - Biological Psychiatry

IS - 2

ER -

Genome-wide Association Study points to novel locus for Gilles de la Tourette Syndrome

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