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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                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009518) 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\u2013compulsive 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                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene\u2013environment 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\u2013environment studies.\n                  <\/jats:p>","DOI":"10.1007\/s00702-021-02396-y","type":"journal-article","created":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T12:02:32Z","timestamp":1628856152000},"page":"1757-1765","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Investigation of gene\u2013environment interactions in relation to tic 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Mathews and Scharf are on the scientific advisory board of the Tourette Association of America (TAA) and have received travel and Grant support from the TAA. Dr. Mathews is also on the scientific advisory board of the International Obsessive\u2013Compulsive Disorder Foundation and the Family Foundation for OCD Research. Dr. Scharf is on the scientific advisory board of the TLC Foundation for Body-Focused Repetitive Behaviors and has received consulting fees from Nuvelution Pharma and Abide Pharmaceuticals. Dr. Coffey is co-Chair of the TAA Medical Advisory Board and has received honoraria from the TAA-CDC partnership She has also received honoraria from the American Academy of Child and Adolescent Psychiatry, Partners Health Care, Harvard Medical School\/Psychiatry Academy; consulting fees fromTeva\/Nuvelution, and Skyland Trail, and research support from NIMH and Emalex Pharmaceuticals. The remaining authors reported no biomedical financial interest or potential conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All adult participants and parents of children provided written informed consent along with written or oral assent of their participating child. The Institutional Review Board of each participating site had approved the study which are: 1. University of Groningen 2. Yale Child Study Center 3. Childrens Hospital of Philadelphia 4. Yonsei University College of Medicine 5. Icahn School of Medicine at Mount Sinai 6. Nathan S. Kline Institute for Psychiatric Research 7. Yulius Mental Health Organization 8. Medizinische Hochschule Hannover Klinik fur Psychiatrie 9. University Hospital Medical Center Hamburg-Eppendorf 10. Hospital Clinic Universitari 11. Cincinnati Childrens Hospital Medical Center 12. Evelina London Childrens Hospital GSTT 13. Great Ormond Street Hospital for Children and UCL Institute of Child Health 14. Hallym University Sacred Heart Hospital 15. De Bascule 16. Amsterdam Academic Medical Center 17. Yonsei Bom Clinic 18. University of California San Francisco 19. Korea Institute for Childrens Social Development 20. Kangbuk Samsung Hospital 21. University of Iowa Carver College of Medicine Iowa City 22. University of Ulm 23. Universidad de Sevilla 24. Erasmus Medical Center-Sophia Childrens Hospital Rotterdam 25. Institut de Investigacions Biomediques August Pi i Sunyer (IDIPABS) and Centro de Investigacion en Red de Salud Mental (CIBERSAM) 26. University of Lubeck 27. University of Copenhagen 28. TU Dresden 29. National Health Insurance Service Ilsan Hospital 30. Altrecht Institute for Mental Health 31. Admiraal De Ruyter Ziekenhuis 32. University of Washington Seattle.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"As stated above.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"All participants agreed on the use and publication of anonymized data.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}