학술논문
Investigation of gene–environment interactions in relation to tic severity
Document Type
Original Paper
Author
Abdulkadir, Mohamed; Yu, Dongmei; Osiecki, Lisa; King, Robert A.; Fernandez, Thomas V.; Brown, Lawrence W.; Cheon, Keun-Ah; Coffey, Barbara J.; Garcia-Delgar, Blanca; Gilbert, Donald L.; Grice, Dorothy E.; Hagstrøm, Julie; Hedderly, Tammy; Heyman, Isobel; Hong, Hyun Ju; Huyser, Chaim; Ibanez-Gomez, Laura; Kim, Young Key; Kim, Young-Shin; Koh, Yun-Joo; Kook, Sodahm; Kuperman, Samuel; Leventhal, Bennett; Madruga-Garrido, Marcos; Maras, Athanasios; Mir, Pablo; Morer, Astrid; Münchau, Alexander; Plessen, Kerstin J.; Roessner, Veit; Shin, Eun-Young; Song, Dong-Ho; Song, Jungeun; Visscher, Frank; Zinner, Samuel H.; Mathews, Carol A.; Scharf, Jeremiah M.; Tischfield, Jay A.; Heiman, Gary A.; Dietrich, Andrea; Hoekstra, Pieter J.
Source
Journal of Neural Transmission: Translational Neuroscience, Neurology and Preclinical Neurological Studies, Psychiatry and Preclinical Psychiatric Studies. 128(11):1757-1765
Subject
Language
English
ISSN
0300-9564
1435-1463
1435-1463
Abstract
Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive–compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene–environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene–environment studies.