Investigation of previously implicated genetic variants in chronic tic disorders: a transmission disequilibrium test approach
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Investigation of previously implicated genetic variants in chronic tic disorders: a transmission disequilibrium test approach. / 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; Kim, Young Key; Kim, Young Shin; Koh, Yun-Joo; Kook, Sodahm; Kuperman, Samuel; Leventhal, Bennett; Ludolph, Andrea G; Madruga-Garrido, Marcos; Maras, Athanasios; Mir, Pablo; Morer, Astrid; Müller-Vahl, Kirsten; Münchau, Alexander; Murphy, Tara L; Plessen, Kerstin J; Roessner, Veit; Shin, Eun-Young; Song, Dong-Ho; Song, Jungeun; Tübing, Jennifer; van den Ban, Els; Visscher, Frank; Wanderer, Sina; Woods, Martin; Zinner, Samuel H; King, Robert A; Tischfield, Jay A; Heiman, Gary A; Hoekstra, Pieter J; Dietrich, Andrea.
In: EUR ARCH PSY CLIN N, Vol. 268, No. 3, 04.2018, p. 301-316.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Investigation of previously implicated genetic variants in chronic tic disorders: a transmission disequilibrium test approach
AU - Abdulkadir, Mohamed
AU - Londono, Douglas
AU - Gordon, Derek
AU - Fernandez, Thomas V
AU - Brown, Lawrence W
AU - Cheon, Keun-Ah
AU - Coffey, Barbara J
AU - Elzerman, Lonneke
AU - Fremer, Carolin
AU - Fründt, Odette
AU - Garcia-Delgar, Blanca
AU - Gilbert, Donald L
AU - Grice, Dorothy E
AU - Hedderly, Tammy
AU - Heyman, Isobel
AU - Hong, Hyun Ju
AU - Huyser, Chaim
AU - Ibanez-Gomez, Laura
AU - Jakubovski, Ewgeni
AU - Kim, Young Key
AU - Kim, Young Shin
AU - Koh, Yun-Joo
AU - Kook, Sodahm
AU - Kuperman, Samuel
AU - Leventhal, Bennett
AU - Ludolph, Andrea G
AU - Madruga-Garrido, Marcos
AU - Maras, Athanasios
AU - Mir, Pablo
AU - Morer, Astrid
AU - Müller-Vahl, Kirsten
AU - Münchau, Alexander
AU - Murphy, Tara L
AU - Plessen, Kerstin J
AU - Roessner, Veit
AU - Shin, Eun-Young
AU - Song, Dong-Ho
AU - Song, Jungeun
AU - Tübing, Jennifer
AU - van den Ban, Els
AU - Visscher, Frank
AU - Wanderer, Sina
AU - Woods, Martin
AU - Zinner, Samuel H
AU - King, Robert A
AU - Tischfield, Jay A
AU - Heiman, Gary A
AU - Hoekstra, Pieter J
AU - Dietrich, Andrea
PY - 2018/4
Y1 - 2018/4
N2 - 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.
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.
KW - Journal Article
U2 - 10.1007/s00406-017-0808-8
DO - 10.1007/s00406-017-0808-8
M3 - SCORING: Journal article
C2 - 28555406
VL - 268
SP - 301
EP - 316
JO - EUR ARCH PSY CLIN N
JF - EUR ARCH PSY CLIN N
SN - 0940-1334
IS - 3
ER -