Priority CommunicationRare Copy Number Variants in Tourette Syndrome Disrupt Genes in Histaminergic Pathways and Overlap with Autism
Section snippets
Study Subjects
Patients who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for Tourette's disorder (50) and their parents, if available, were included. Two cohorts of Caucasian TS patients (n = 645, including 248 trios) from independent studies in the United States and Netherlands were ascertained (see Supplementary Methods in Supplement 1). Control subjects were comprised of unrelated children (n = 546) and parents (n = 1098) of European ancestry from the
Results
After completing quality control and case-control matching, a total of 460 cases (148 trios) and 1131 control subjects (436 trios) were included in our analyses (Figure 1; see also Table S1 and Figures S1 and S2 in Supplement 1). Principal component analysis of genotypic data yielded a genomic inflation factor (λ) of 1.14. We further corrected for residual differences in batch effects by adjusting LogR values for nine principal components (Figure S3 in Supplement 1). From this matched sample,
Discussion
Our data support recent findings implicating histaminergic neurotransmission in the etiology or modulation of tics and highlight the potential involvement of GABAergic mechanisms as well. In addition, the results reinforce the notion of shared genetic risks among clinically distinct syndromes, in this case ASD and tic disorders, and identify three novel, large, rare, genic de novo CNVs that are likely carrying risk in the individuals in which they were identified, based on their de novo status
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