1. Investigation of gene-environment interactions in relation to tic severity
- Author
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Frank Visscher, Kerstin J. Plessen, Tammy Hedderly, Jungeun Song, Bennett L. Leventhal, Eun-Young Shin, Lawrence W. Brown, Alexander Münchau, Robert A. King, Young Key Kim, Young Shin Kim, Veit Roessner, Andrea Dietrich, Samuel Kuperman, Thomas V. Fernandez, Keun-Ah Cheon, Carol A. Mathews, Athanasios Maras, Donald L. Gilbert, Yun-Joo Koh, Laura Ibanez-Gomez, Dongmei Yu, Astrid Morer, Sodahm Kook, Marcos Madruga-Garrido, Julie Hagstrøm, Dorothy E. Grice, Jay A. Tischfield, Lisa Osiecki, Mohamed Abdulkadir, Blanca Garcia-Delgar, Samuel H. Zinner, Chaim Huyser, Barbara J. Coffey, Dong-Ho Song, Gary A. Heiman, Pieter J. Hoekstra, Hyun Ju Hong, Pablo Mir, Isobel Heyman, Jeremiah M. Scharf, National Institute of Mental Health (US), Tourette Syndrome Association of New Jersey, Judah Foundation, Tourette Association of America, National Institutes of Health (US), Instituto de Salud Carlos III, Junta de Andalucía, Sociedad Andaluza de Neurología, Fundación Alicia Koplowitz, Fundación Mutua Madrileña, Jacques and Gloria Gossweiler Foundation, Generalitat de Catalunya, German Research Foundation, National Institute of Environmental Health Sciences (US), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Child Psychiatry, Paediatric Psychosocial Care, and Amsterdam Neuroscience - Cellular & Molecular Mechanisms
- Subjects
Candidate gene ,Tic severity ,Autism Spectrum Disorder ,Autism ,Intellectual and Developmental Disabilities (IDD) ,Single-nucleotide polymorphism ,Genome-wide association study ,Neurodegenerative ,Tourette syndrome ,Severity of Illness Index ,Attention Deficit Disorder with Hyperactivity/genetics ,Autism Spectrum Disorder/genetics ,Female ,Gene-Environment Interaction ,Genome-Wide Association Study ,Humans ,Pregnancy ,Tics ,Tourette Syndrome ,Gene–environment interaction ,Pre- and perinatal complications ,mental disorders ,medicine ,Genetics ,SNP ,2.1 Biological and endogenous factors ,Psychology ,Aetiology ,Biological Psychiatry ,Genetic association ,Pediatric ,Neurology & Neurosurgery ,business.industry ,Psychiatry and Preclinical Psychiatric Studies - Original Article ,Human Genome ,Neurosciences ,medicine.disease ,Serious Mental Illness ,Gene-environment interaction ,Brain Disorders ,Psychiatry and Mental health ,Mental Health ,Neurology ,Autism spectrum disorder ,Attention Deficit Disorder with Hyperactivity ,Neurology (clinical) ,business - 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., This research was funded by National Institute of Mental Health (NIMH) grant R01MH092293 (to GAH and JAT) and NJCTS (New Jersey Center for Tourette Syndrome and Associated Disorders; to GAH and JAT). This work was also supported by grants from the Judah Foundation, the Tourette Association of America, National Institute of Health (NIH) Grants NS40024, NS016648, MH079489, MH073250, the American Recovery and Re-investment Act (ARRA) Grants NS040024-07S1; NS16648-29S1; NS040024-09S1; MH092289; MH092290; MH092291; MH092292; R01MH092293; MH092513; MH092516; MH092520; MH071507; MH079489; MH079487; MH079488; and MH079494. Dr. Mir has received grants from the Instituto de Salud Carlos III (PI10/01674, PI13/01461), the Consejería de Economía, Innovación, Ciencia y Empresa de la Junta de Andalucía (CVI-02526, CTS-7685), the Consejería de Salud y Bienestar Social de la Junta de Andalucía (PI-0741/2010, PI-0437-2012, PI-0471-2013), the Sociedad Andaluza de Neurología, the Fundación Alicia Koplowitz, the Fundación Mutua Madrileña and the Jaques and Gloria Gossweiler Foundation. Dr. Morer has received grants from the Fundacion Alicia Koplowitz and belongs to the research group of the Comissionat per Universitats i Recerca del Departmanent d’Innovacio (DIUE) 2009SGR1119. Dr. Münchau has received grants from the Deutsche Forschungsgemeinschaft (DFG: MU 1692/3-1, MU 1692/4-1 and FOR 2698). This study was also supported by a Grant from the National Institute for Environmental Health Science (R01 ES021462).
- Published
- 2021