Association of intronic variants of the BTBD9 gene with Tourette syndrome.
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.


METHODS
Case-control association study.


METHODS
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.


METHODS
Clinical diagnosis of TS, obsessive-compulsive disorder, and attention-deficit disorder.


RESULTS
The study provided 3 single-nucleotide polymorphisms within BTBD9 associated with TS (chi(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 (chi(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.


CONCLUSIONS
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.
Rivière
Jean-Baptiste
JB
Sainte Justine Hospital Research Center and the Center of Excellence in Neuromics, University of Montreal, Montreal, QC H2L 4M1, Canada.
Xiong
Lan
L
Levchenko
Anastasia
A
St-Onge
Judith
J
Gaspar
Claudia
C
Dion
Yves
Y
Lespérance
Paul
P
Tellier
Geneviève
G
Richer
François
F
Chouinard
Sylvain
S
Rouleau
Guy A
GA
D000328:Adult; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000235:genetics / Q000523:psychology; D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D005190:Family; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics*; D008297:Male; D009419:Nerve Tissue Proteins; D009483:Neuropsychological Tests; D020189:Nocturnal Myoclonus Syndrome / Q000235:genetics / Q000523:psychology; D009771:Obsessive-Compulsive Disorder / Q000150:complications / Q000235:genetics / Q000523:psychology; D017063:Outcome Assessment, Health Care; D020641:Polymorphism, Single Nucleotide; D012148:Restless Legs Syndrome / Q000235:genetics / Q000523:psychology; D018570:Risk Assessment; D005879:Tourette Syndrome / Q000150:complications / Q000235:genetics* / Q000523:psychology; D014157:Transcription Factors / Q000235:genetics*
C522207:BTBD9 protein, human; D009419:Nerve Tissue Proteins; D014157:Transcription Factors