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Family‐based genetic association study of DLGAP3 in Tourette Syndrome
Author(s) -
Crane Jacquelyn,
Fagerness Jesen,
Osiecki Lisa,
Gunnell Boyd,
Stewart S. Evelyn,
Pauls David L.,
Scharf Jeremiah M.
Publication year - 2011
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.31134
Subject(s) - tourette syndrome , candidate gene , haplotype , single nucleotide polymorphism , transmission disequilibrium test , genetics , genetic association , tics , glutamatergic , psychology , gene , biology , allele , genotype , neuroscience , glutamate receptor , psychiatry , receptor
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. © 2010 Wiley‐Liss, Inc.