Investigation of previously implicated genetic variants in chronic tic disorders: a transmission disequilibrium test approach.
Details
Serval ID
serval:BIB_B13AC350DE85
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Investigation of previously implicated genetic variants in chronic tic disorders: a transmission disequilibrium test approach.
Journal
European archives of psychiatry and clinical neuroscience
ISSN
1433-8491 (Electronic)
ISSN-L
0940-1334
Publication state
Published
Issued date
04/2018
Peer-reviewed
Oui
Volume
268
Number
3
Pages
301-316
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
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.
Keywords
Adolescent, Adult, Child, Child, Preschool, Family Health, Female, Genome-Wide Association Study, Genotype, Humans, Linkage Disequilibrium, Male, Microtubule-Associated Proteins/genetics, Middle Aged, Polymorphism, Single Nucleotide/genetics, Severity of Illness Index, Tic Disorders/genetics, Tryptophan Hydroxylase/genetics, Young Adult, Attention-deficit/hyperactivity disorder, Candidate gene study, Obsessive–compulsive disorder, Tourette syndrome, Transmission Disequilibrium Test
Pubmed
Web of science
Open Access
Yes
Create date
12/02/2019 9:42
Last modification date
20/08/2019 15:20