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Jean-Baptiste Rivière, MSc; Lan Xiong, MD, PhD; Anastasia Levchenko, PhD; Judith St-Onge, DEC; Claudia Gaspar, PhD; Yves Dion, MD; Paul Lespérance, MD; Geneviève Tellier, MD; François Richer, PhD; Sylvain Chouinard, MD; Guy A. Rouleau, MD, PhD; for the Montreal Tourette Study Group

Arch Neurol. 2009;66(10):1267-1272.

Objective  To test the association between Tourette syndrome (TS) and genetic variants in genomic loci MEIS1, MAP2K5/LBXCOR1, and BTBD9, for which genome-wide association studies in restless legs syndrome and periodic limb movements during sleep revealed common risk variants.

Design  Case-control association study.

Setting  Movement disorder clinic in Montreal.

Subjects  We typed 14 single-nucleotide polymorphisms spanning the 3 genomic loci in 298 TS trios, 322 TS cases (including 298 probands from the cohort of TS trios), and 290 control subjects.

Main Outcome Measures  Clinical diagnosis of TS, obsessive-compulsive disorder, and attention-deficit disorder.

Results  The study provided 3 single-nucleotide polymorphisms within BTBD9 associated with TS (² = 8.02 [P = .005] for rs9357271), with the risk alleles for restless legs syndrome and periodic limb movements during sleep overrepresented in the TS cohort. We stratified our group of patients with TS according to presence or absence of obsessive-compulsive disorder and/or attention-deficit disorder and found that variants in BTBD9 were strongly associated with TS without obsessive-compulsive disorder (² = 12.95 [P < .001] for rs9357271). Furthermore, allele frequency of rs9357271 inversely correlated with severity of obsessive-compulsive disorder as measured by the Yale-Brown Obsessive Compulsive Scale score.

Conclusion  Variants in BTBD9 that predispose to restless legs syndrome and periodic limb movements during sleep are also associated with TS, particularly TS without obsessive-compulsive disorder.

Author Affiliations: Center of Excellence in Neuromics, University of Montreal Hospital Center and Sainte-Justine Hospital, Montreal, Quebec, Canada.

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