Genetic association signal near NTN4 in Tourette syndrome

Peristera Paschou; Dongmei Yu; Gloria Gerber; Patrick Evans; Fotis Tsetsos; Lea K. Davis; Iordanis Karagiannidis; Jonathan Chaponis; Eric Gamazon; Kirsten Mueller-Vahl; Manfred Stuhrmann; Monika Schloegelhofer; Mara Stamenkovic; Johannes Hebebrand; Markus Noethen; Peter Nagy; Csaba Barta; Zsanett Tarnok; Renata Rizzo; Christel Depienne; Yulia Worbe; Andreas Hartmann; Danielle C. Cath; Cathy L. Budman; Paul Sandor; Cathy Barr; Thomas Wolanczyk; Harvey Singer; I. Ching Chou; Marco Grados; Danielle Posthuma; Guy A. Rouleau; Harald Aschauer; Nelson B. Freimer; David L. Pauls; Nancy J. Cox; Carol A. Mathews; Jeremiah M. Scharf

doi:10.1002/ana.24215

Genetic association signal near NTN4 in Tourette syndrome

Peristera Paschou, Dongmei Yu, Gloria Gerber, Patrick Evans, Fotis Tsetsos, Lea K. Davis, Iordanis Karagiannidis, Jonathan Chaponis, Eric Gamazon, Kirsten Mueller-Vahl, Manfred Stuhrmann, Monika Schloegelhofer, Mara Stamenkovic, Johannes Hebebrand, Markus Noethen, Peter Nagy, Csaba Barta, Zsanett Tarnok, Renata Rizzo, Christel DepienneYulia Worbe, Andreas Hartmann, Danielle C. Cath, Cathy L. Budman, Paul Sandor, Cathy Barr, Thomas Wolanczyk, Harvey Singer, I. Ching Chou, Marco Grados, Danielle Posthuma, Guy A. Rouleau, Harald Aschauer, Nelson B. Freimer, David L. Pauls, Nancy J. Cox, Carol A. Mathews, Jeremiah M. Scharf

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Abstract

Tourette syndrome (TS) is a neurodevelopmental disorder with a complex genetic etiology. Through an international collaboration, we genotyped 42 single nucleotide polymorphisms (p < 10^-3) from the recent TS genomewide association study (GWAS) in 609 independent cases and 610 ancestry-matched controls. Only rs2060546 on chromosome 12q22 (p = 3.3 × 10^-4) remained significant after Bonferroni correction. Meta-analysis with the original GWAS yielded the strongest association to date (p = 5.8 × 10 ^-7). Although its functional significance is unclear, rs2060546 lies closest to NTN4, an axon guidance molecule expressed in developing striatum. Risk score analysis significantly predicted case-control status (p = 0.042), suggesting that many of these variants are true TS risk alleles.

Original language	English (US)
Pages (from-to)	310-315
Number of pages	6
Journal	Annals of neurology
Volume	76
Issue number	2
DOIs	https://doi.org/10.1002/ana.24215
State	Published - Aug 2014

ASJC Scopus subject areas

Neurology
Clinical Neurology

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Paschou, P., Yu, D., Gerber, G., Evans, P., Tsetsos, F., Davis, L. K., Karagiannidis, I., Chaponis, J., Gamazon, E., Mueller-Vahl, K., Stuhrmann, M., Schloegelhofer, M., Stamenkovic, M., Hebebrand, J., Noethen, M., Nagy, P., Barta, C., Tarnok, Z., Rizzo, R., ... Scharf, J. M. (2014). Genetic association signal near NTN4 in Tourette syndrome. Annals of neurology, 76(2), 310-315. https://doi.org/10.1002/ana.24215

Paschou, P, Yu, D, Gerber, G, Evans, P, Tsetsos, F, Davis, LK, Karagiannidis, I, Chaponis, J, Gamazon, E, Mueller-Vahl, K, Stuhrmann, M, Schloegelhofer, M, Stamenkovic, M, Hebebrand, J, Noethen, M, Nagy, P, Barta, C, Tarnok, Z, Rizzo, R, Depienne, C, Worbe, Y, Hartmann, A, Cath, DC, Budman, CL, Sandor, P, Barr, C, Wolanczyk, T, Singer, H, Chou, IC, Grados, M, Posthuma, D, Rouleau, GA, Aschauer, H, Freimer, NB, Pauls, DL, Cox, NJ, Mathews, CA & Scharf, JM 2014, 'Genetic association signal near NTN4 in Tourette syndrome', Annals of neurology, vol. 76, no. 2, pp. 310-315. https://doi.org/10.1002/ana.24215

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title = "Genetic association signal near NTN4 in Tourette syndrome",

abstract = "Tourette syndrome (TS) is a neurodevelopmental disorder with a complex genetic etiology. Through an international collaboration, we genotyped 42 single nucleotide polymorphisms (p < 10-3) from the recent TS genomewide association study (GWAS) in 609 independent cases and 610 ancestry-matched controls. Only rs2060546 on chromosome 12q22 (p = 3.3 × 10-4) remained significant after Bonferroni correction. Meta-analysis with the original GWAS yielded the strongest association to date (p = 5.8 × 10 -7). Although its functional significance is unclear, rs2060546 lies closest to NTN4, an axon guidance molecule expressed in developing striatum. Risk score analysis significantly predicted case-control status (p = 0.042), suggesting that many of these variants are true TS risk alleles.",

author = "Peristera Paschou and Dongmei Yu and Gloria Gerber and Patrick Evans and Fotis Tsetsos and Davis, {Lea K.} and Iordanis Karagiannidis and Jonathan Chaponis and Eric Gamazon and Kirsten Mueller-Vahl and Manfred Stuhrmann and Monika Schloegelhofer and Mara Stamenkovic and Johannes Hebebrand and Markus Noethen and Peter Nagy and Csaba Barta and Zsanett Tarnok and Renata Rizzo and Christel Depienne and Yulia Worbe and Andreas Hartmann and Cath, {Danielle C.} and Budman, {Cathy L.} and Paul Sandor and Cathy Barr and Thomas Wolanczyk and Harvey Singer and Chou, {I. Ching} and Marco Grados and Danielle Posthuma and Rouleau, {Guy A.} and Harald Aschauer and Freimer, {Nelson B.} and Pauls, {David L.} and Cox, {Nancy J.} and Mathews, {Carol A.} and Scharf, {Jeremiah M.}",

year = "2014",

month = aug,

doi = "10.1002/ana.24215",

language = "English (US)",

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AU - Paschou, Peristera

AU - Yu, Dongmei

AU - Gerber, Gloria

AU - Evans, Patrick

AU - Tsetsos, Fotis

AU - Davis, Lea K.

AU - Karagiannidis, Iordanis

AU - Chaponis, Jonathan

AU - Gamazon, Eric

AU - Mueller-Vahl, Kirsten

AU - Stuhrmann, Manfred

AU - Schloegelhofer, Monika

AU - Stamenkovic, Mara

AU - Hebebrand, Johannes

AU - Noethen, Markus

AU - Nagy, Peter

AU - Barta, Csaba

AU - Tarnok, Zsanett

AU - Rizzo, Renata

AU - Depienne, Christel

AU - Worbe, Yulia

AU - Hartmann, Andreas

AU - Cath, Danielle C.

AU - Budman, Cathy L.

AU - Sandor, Paul

AU - Barr, Cathy

AU - Wolanczyk, Thomas

AU - Singer, Harvey

AU - Chou, I. Ching

AU - Grados, Marco

AU - Posthuma, Danielle

AU - Rouleau, Guy A.

AU - Aschauer, Harald

AU - Freimer, Nelson B.

AU - Pauls, David L.

AU - Cox, Nancy J.

AU - Mathews, Carol A.

AU - Scharf, Jeremiah M.

PY - 2014/8

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AB - Tourette syndrome (TS) is a neurodevelopmental disorder with a complex genetic etiology. Through an international collaboration, we genotyped 42 single nucleotide polymorphisms (p < 10-3) from the recent TS genomewide association study (GWAS) in 609 independent cases and 610 ancestry-matched controls. Only rs2060546 on chromosome 12q22 (p = 3.3 × 10-4) remained significant after Bonferroni correction. Meta-analysis with the original GWAS yielded the strongest association to date (p = 5.8 × 10 -7). Although its functional significance is unclear, rs2060546 lies closest to NTN4, an axon guidance molecule expressed in developing striatum. Risk score analysis significantly predicted case-control status (p = 0.042), suggesting that many of these variants are true TS risk alleles.

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Genetic association signal near NTN4 in Tourette syndrome

Abstract

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