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A recent TS genome-wide association study (GWAS) identified a genome-wide significant locus. However, determining the biological mechanism of GWAS signals remains difficult. To characterize effects of expression quantitative trait loci (eQTLs) in TS and understand biological underpinnings of the disease. Here, we conduct a TS transcriptome-wide association study (TWAS) consisting of 4819 cases and 9488 controls. We demonstrate that increased expression of<jats:italic>FLT3<\/jats:italic>in the dorsolateral prefrontal cortex (DLPFC) is associated with TS. We further show that there is global dysregulation of<jats:italic>FLT3<\/jats:italic>across several brain regions and probabilistic causal fine-mapping of the TWAS signal prioritizes<jats:italic>FLT3<\/jats:italic>with a posterior inclusion probability of 0.849. After, we proxy the expression with 100 lymphoblastoid cell lines, and demonstrate that TS cells has a 1.72 increased fold change compared to controls. A phenome-wide association study also points toward<jats:italic>FLT3<\/jats:italic>having links with immune-related pathways such as monocyte count. We further identify several splicing events in<jats:italic>MPHOSPH9<\/jats:italic>,<jats:italic>CSGALNACT2<\/jats:italic>and<jats:italic>FIP1L1<\/jats:italic>associated with TS, which are also implicated in immune function. This analysis of expression and splicing begins to explore the biology of TS GWAS signals.<\/jats:p>","DOI":"10.1038\/s42003-022-03231-0","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T10:03:31Z","timestamp":1648634611000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Transcriptome-wide association study reveals increased neuronal FLT3 expression is associated with Tourette\u2019s syndrome"],"prefix":"10.1038","volume":"5","author":[{"given":"Calwing","family":"Liao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veikko","family":"Vuokila","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9l\u00e8ne","family":"Catoire","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0931-5247","authenticated-orcid":false,"given":"Fulya","family":"Ak\u00e7imen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8183-2524","authenticated-orcid":false,"given":"Jay P.","family":"Ross","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia V.","family":"Bourassa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick A.","family":"Dion","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inge A.","family":"Meijer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8403-1418","authenticated-orcid":false,"given":"Guy A.","family":"Rouleau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,3,30]]},"reference":[{"key":"3231_CR1","doi-asserted-by":"publisher","first-page":"161","DOI":"10.31887\/DCNS.2007.9.2\/nmueller","volume":"9","author":"N M\u00fcller","year":"2007","unstructured":"M\u00fcller, N. 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