Family-based genetic association study of DLGAP3 in Tourette Syndrome

Jacquelyn Crane, Jesen Fagerness, Lisa Osiecki, Boyd Gunnell, S. Evelyn Stewart, David L. Pauls, Jeremiah M. Scharf*, D. Cath, P. Heutink, M. Grados, H. S. Singer, J. T. Walkup, Scharf J.M. Scharf, C. Illmann, D. Yu, J. Platko, S. Santangelo, S. E. Stewart, D. L. Pauls, N. J. Cox & 27 others S. Service, D. Keen-Kim, C. Sabatti, N. Freimer, M. M. Robertson, G. A. Rouleau, J. B. Riviere, S. Chouinard, F. Richer, P. Lesperance, Y. Dion, R. A. King, J. R. Kidd, A. J. Pakstis, J. F. Leckman, K. K. Kidd, R. Kurlan, P. Como, D. Palumbo, A. Verkerk, B. A. Oostra, W. McMahon, M. Leppert, H. Coon, C. Mathews, P. Sandor, C. L. Barr

*Corresponding author for this work

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder that is familial and highly heritable. Although genetic influences are thought to play a significant role in the development of TS, no definite TS susceptibility genes have been identified to date. TS is believed to be genetically related to both obsessive-compulsive disorder (OCD) and grooming disorders (GD) such as trichotillomania (TTM). SAP90/PSD95-associated protein 3 (SAPAP3/DLGAP3) is a post-synaptic scaffolding protein that is highly expressed in glutamatergic synapses in the striatum and has recently been investigated as a candidate gene in both OCD and GD studies. Given the shared familial relationship between TS, OCD and TTM, DLGAP3 was evaluated as a candidate TS susceptibility gene. In a family-based sample of 289 TS trios, 22 common single nucleotide polymorphisms (SNPs) in the DLGAP3 region were analyzed. Nominally significant associations were identified between TS and rs11264126 and two haplotypes containing rs11264126 and rs12141243. Secondary analyses demonstrated that these results cannot be explained by the presence of comorbid OCD or TTM in the sample. Although none of these results remained significant after correction for multiple hypothesis testing, DLGAP3 remains a promising candidate gene for TS.

Original languageEnglish (US)
Pages (from-to)108-114
Number of pages7
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume156
Issue number1
DOIs
StatePublished - Jan 1 2011

Fingerprint

Tourette Syndrome
Genetic Association Studies
Obsessive-Compulsive Disorder
Trichotillomania
Grooming
Genes
Synapses
Haplotypes
Single Nucleotide Polymorphism
Proteins

Keywords

  • Gene
  • Glutamate
  • SAPAP3
  • Tic disorders
  • Trichotillomania

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Crane, J., Fagerness, J., Osiecki, L., Gunnell, B., Stewart, S. E., Pauls, D. L., ... Barr, C. L. (2011). Family-based genetic association study of DLGAP3 in Tourette Syndrome. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 156(1), 108-114. https://doi.org/10.1002/ajmg.b.31134
Crane, Jacquelyn ; Fagerness, Jesen ; Osiecki, Lisa ; Gunnell, Boyd ; Stewart, S. Evelyn ; Pauls, David L. ; Scharf, Jeremiah M. ; Cath, D. ; Heutink, P. ; Grados, M. ; Singer, H. S. ; Walkup, J. T. ; J.M. Scharf, Scharf ; Illmann, C. ; Yu, D. ; Platko, J. ; Santangelo, S. ; Stewart, S. E. ; Pauls, D. L. ; Cox, N. J. ; Service, S. ; Keen-Kim, D. ; Sabatti, C. ; Freimer, N. ; Robertson, M. M. ; Rouleau, G. A. ; Riviere, J. B. ; Chouinard, S. ; Richer, F. ; Lesperance, P. ; Dion, Y. ; King, R. A. ; Kidd, J. R. ; Pakstis, A. J. ; Leckman, J. F. ; Kidd, K. K. ; Kurlan, R. ; Como, P. ; Palumbo, D. ; Verkerk, A. ; Oostra, B. A. ; McMahon, W. ; Leppert, M. ; Coon, H. ; Mathews, C. ; Sandor, P. ; Barr, C. L. / Family-based genetic association study of DLGAP3 in Tourette Syndrome. In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 2011 ; Vol. 156, No. 1. pp. 108-114.
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Crane, J, Fagerness, J, Osiecki, L, Gunnell, B, Stewart, SE, Pauls, DL, Scharf, JM, Cath, D, Heutink, P, Grados, M, Singer, HS, Walkup, JT, J.M. Scharf, S, Illmann, C, Yu, D, Platko, J, Santangelo, S, Stewart, SE, Pauls, DL, Cox, NJ, Service, S, Keen-Kim, D, Sabatti, C, Freimer, N, Robertson, MM, Rouleau, GA, Riviere, JB, Chouinard, S, Richer, F, Lesperance, P, Dion, Y, King, RA, Kidd, JR, Pakstis, AJ, Leckman, JF, Kidd, KK, Kurlan, R, Como, P, Palumbo, D, Verkerk, A, Oostra, BA, McMahon, W, Leppert, M, Coon, H, Mathews, C, Sandor, P & Barr, CL 2011, 'Family-based genetic association study of DLGAP3 in Tourette Syndrome', American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, vol. 156, no. 1, pp. 108-114. https://doi.org/10.1002/ajmg.b.31134

Family-based genetic association study of DLGAP3 in Tourette Syndrome. / Crane, Jacquelyn; Fagerness, Jesen; Osiecki, Lisa; Gunnell, Boyd; Stewart, S. Evelyn; Pauls, David L.; Scharf, Jeremiah M.; Cath, D.; Heutink, P.; Grados, M.; Singer, H. S.; Walkup, J. T.; J.M. Scharf, Scharf; Illmann, C.; Yu, D.; Platko, J.; Santangelo, S.; Stewart, S. E.; Pauls, D. L.; Cox, N. J.; Service, S.; Keen-Kim, D.; Sabatti, C.; Freimer, N.; Robertson, M. M.; Rouleau, G. A.; Riviere, J. B.; Chouinard, S.; Richer, F.; Lesperance, P.; Dion, Y.; King, R. A.; Kidd, J. R.; Pakstis, A. J.; Leckman, J. F.; Kidd, K. K.; Kurlan, R.; Como, P.; Palumbo, D.; Verkerk, A.; Oostra, B. A.; McMahon, W.; Leppert, M.; Coon, H.; Mathews, C.; Sandor, P.; Barr, C. L.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 156, No. 1, 01.01.2011, p. 108-114.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Family-based genetic association study of DLGAP3 in Tourette Syndrome

AU - Crane, Jacquelyn

AU - Fagerness, Jesen

AU - Osiecki, Lisa

AU - Gunnell, Boyd

AU - Stewart, S. Evelyn

AU - Pauls, David L.

AU - Scharf, Jeremiah M.

AU - Cath, D.

AU - Heutink, P.

AU - Grados, M.

AU - Singer, H. S.

AU - Walkup, J. T.

AU - J.M. Scharf, Scharf

AU - Illmann, C.

AU - Yu, D.

AU - Platko, J.

AU - Santangelo, S.

AU - Stewart, S. E.

AU - Pauls, D. L.

AU - Cox, N. J.

AU - Service, S.

AU - Keen-Kim, D.

AU - Sabatti, C.

AU - Freimer, N.

AU - Robertson, M. M.

AU - Rouleau, G. A.

AU - Riviere, J. B.

AU - Chouinard, S.

AU - Richer, F.

AU - Lesperance, P.

AU - Dion, Y.

AU - King, R. A.

AU - Kidd, J. R.

AU - Pakstis, A. J.

AU - Leckman, J. F.

AU - Kidd, K. K.

AU - Kurlan, R.

AU - Como, P.

AU - Palumbo, D.

AU - Verkerk, A.

AU - Oostra, B. A.

AU - McMahon, W.

AU - Leppert, M.

AU - Coon, H.

AU - Mathews, C.

AU - Sandor, P.

AU - Barr, C. L.

PY - 2011/1/1

Y1 - 2011/1/1

N2 - Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder that is familial and highly heritable. Although genetic influences are thought to play a significant role in the development of TS, no definite TS susceptibility genes have been identified to date. TS is believed to be genetically related to both obsessive-compulsive disorder (OCD) and grooming disorders (GD) such as trichotillomania (TTM). SAP90/PSD95-associated protein 3 (SAPAP3/DLGAP3) is a post-synaptic scaffolding protein that is highly expressed in glutamatergic synapses in the striatum and has recently been investigated as a candidate gene in both OCD and GD studies. Given the shared familial relationship between TS, OCD and TTM, DLGAP3 was evaluated as a candidate TS susceptibility gene. In a family-based sample of 289 TS trios, 22 common single nucleotide polymorphisms (SNPs) in the DLGAP3 region were analyzed. Nominally significant associations were identified between TS and rs11264126 and two haplotypes containing rs11264126 and rs12141243. Secondary analyses demonstrated that these results cannot be explained by the presence of comorbid OCD or TTM in the sample. Although none of these results remained significant after correction for multiple hypothesis testing, DLGAP3 remains a promising candidate gene for TS.

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