1. Investigation of previously implicated genetic variants in chronic tic disorders: a transmission disequilibrium test approach.
- Author
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Abdulkadir, Mohamed, Londono, Douglas, Gordon, Derek, Fernandez, Thomas V., Brown, Lawrence W., Cheon, Keun-Ah, Coffey, Barbara J., Elzerman, Lonneke, Fremer, Carolin, Fründt, Odette, Garcia-Delgar, Blanca, Gilbert, Donald L., Grice, Dorothy E., Hedderly, Tammy, Heyman, Isobel, Hong, Hyun Ju, Huyser, Chaim, Ibanez-Gomez, Laura, Jakubovski, Ewgeni, and Kim, Young Key
- Subjects
TOURETTE syndrome ,SINGLE nucleotide polymorphisms ,GENETIC testing ,ATTENTION-deficit hyperactivity disorder ,NEUROTRANSMITTERS ,GENETICS - Abstract
Genetic studies in Tourette syndrome (TS) are characterized by scattered and poorly replicated findings. We aimed to replicate findings from candidate gene and genome-wide association studies (GWAS). Our cohort included 465 probands with chronic tic disorder (93% TS) and both parents from 412 families (some probands were siblings). We assessed 75 single nucleotide polymorphisms (SNPs) in 465 parent-child trios; 117 additional SNPs in 211 trios; and 4 additional SNPs in 254 trios. We performed SNP and gene-based transmission disequilibrium tests and compared nominally significant SNP results with those from a large independent case-control cohort. After quality control 71 SNPs were available in 371 trios; 112 SNPs in 179 trios; and 3 SNPs in 192 trios. 17 were candidate SNPs implicated in TS and 2 were implicated in obsessive-compulsive disorder (OCD) or autism spectrum disorder (ASD); 142 were tagging SNPs from eight monoamine neurotransmitter-related genes (including dopamine and serotonin); 10 were top SNPs from TS GWAS; and 13 top SNPs from attention-deficit/hyperactivity disorder, OCD, or ASD GWAS. None of the SNPs or genes reached significance after adjustment for multiple testing. We observed nominal significance for the candidate SNPs rs3744161 (
TBCD ) and rs4565946 (TPH2 ) and for five tagging SNPs; none of these showed significance in the independent cohort. Also,SLC1A1 in our gene-based analysis and two TS GWAS SNPs showed nominal significance, rs11603305 (intergenic) and rs621942 (PICALM ). We found no convincing support for previously implicated genetic polymorphisms. Targeted re-sequencing should fully appreciate the relevance of candidate genes. [ABSTRACT FROM AUTHOR]- Published
- 2018
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