RT Journal Article
T1 Investigation of previously implicated genetic variants in chronic tic disorders: a transmission disequilibrium test approach.
A1 Abdulkadir, Mohamed
A1 Londono, Douglas
A1 Gordon, Derek
A1 Fernandez, Thomas V
A1 Brown, Lawrence W
A1 Cheon, Keun-Ah
A1 Coffey, Barbara J
A1 Elzerman, Lonneke
A1 Fremer, Carolin
A1 Fründt, Odette
A1 Garcia-Delgar, Blanca
A1 Gilbert, Donald L
A1 Grice, Dorothy E
A1 Hedderly, Tammy
A1 Heyman, Isobel
A1 Hong, Hyun Ju
A1 Huyser, Chaim
A1 Ibanez-Gomez, Laura
A1 Jakubovski, Ewgeni
A1 Kim, Young Key
A1 Kim, Young Shin
A1 Koh, Yun-Joo
A1 Kook, Sodahm
A1 Kuperman, Samuel
A1 Leventhal, Bennett
A1 Ludolph, Andrea G
A1 Madruga-Garrido, Marcos
A1 Maras, Athanasios
A1 Mir, Pablo
A1 Morer, Astrid
A1 Müller-Vahl, Kirsten
A1 Münchau, Alexander
A1 Murphy, Tara L
A1 Plessen, Kerstin J
A1 Roessner, Veit
A1 Shin, Eun-Young
A1 Song, Dong-Ho
A1 Song, Jungeun
A1 Tübing, Jennifer
A1 van den Ban, Els
A1 Visscher, Frank
A1 Wanderer, Sina
A1 Woods, Martin
A1 Zinner, Samuel H
A1 King, Robert A
A1 Tischfield, Jay A
A1 Heiman, Gary A
A1 Hoekstra, Pieter J
A1 Dietrich, Andrea
K1 Attention-deficit/hyperactivity disorder
K1 Candidate gene study
K1 Obsessive–compulsive disorder
K1 Tourette syndrome
K1 Transmission Disequilibrium Test
AB 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.
YR 2017
FD 2017-05-29
LK http://hdl.handle.net/10668/11249
UL http://hdl.handle.net/10668/11249
LA en
DS RISalud
RD Apr 6, 2025