Investigation of previously implicated genetic variants in chronic tic disorders: a transmission disequilibrium test approach

• DOI: 10.1007/s00406-017-0808-8
• Publication Date: 2017-05-29T16:08:33Z
• Authors: Mohamed Abdulkadir; Douglas Londono; Derek Gordon; Thomas V. Fernandez; Lawrence W. Brown; Keun-Ah Cheon; Barbara J. Coffey; Lonneke Elzerman; Carolin Fremer; Odette Fründt; Blanca Garcia-Delgar; Donald L. Gilbert; Dorothy E. Grice; Tammy Hedderly; Isobel Heyman; Hyun Ju Hong; Chaim Huyser; Laura Ibanez-Gomez; Ewgeni Jakubovski; Young Key Kim; Young Shin Kim; Yun-Joo Koh; Sodahm Kook; Samuel Kuperman; Bennett Leventhal; Andrea G. Ludolph; Marcos Madruga-Ga...; Athanasios Maras; Pablo Mir; Astrid Morer; Kirsten Müller-Vahl; Alexander Münchau; Tara L. Murphy; Kerstin J. Plessen; Veit Roessner; Eun-Young Shin; Dong-Ho Song; Jungeun Song; Jennifer Tübing; Els van den Ban; Frank Visscher; Sina Wanderer; Martin Woods; Samuel H. Zinner; Robert A. King; Jay A. Tischfield; Gary A. Heiman; Pieter J. Hoekstra; Andrea Dietrich
• Keywords: Transmission disequilibrium test; Genome-wide Association Study; Candidate gene; SNP; Genetic Association; SNP genotyping

Genetic studies in Tourette syndrome (TS) are characterized by scattered and poorly replicated findings. We aimed to replicate findings from candidate gene genome-wide association (GWAS). Our cohort included 465 probands with chronic tic disorder (93% TS) both parents 412 families (some were siblings). assessed 75 single nucleotide polymorphisms (SNPs) parent-child trios; 117 additional SNPs 211 4 254 trios. performed SNP gene-based transmission disequilibrium tests compared nominally significant results those a large independent case-control cohort. After quality control 71 available 371 112 179 3 192 17 implicated TS 2 obsessive-compulsive (OCD) or autism spectrum (ASD); 142 tagging eight monoamine neurotransmitter-related genes (including dopamine serotonin); 10 top GWAS; 13 attention-deficit/hyperactivity disorder, OCD, ASD GWAS. None of the reached significance after adjustment for multiple testing. observed nominal rs3744161 (TBCD) rs4565946 (TPH2) five SNPs; none these showed Also, SLC1A1 our analysis two GWAS significance, rs11603305 (intergenic) rs621942 (PICALM). found no convincing support previously genetic polymorphisms. Targeted re-sequencing should fully appreciate relevance genes.