Abdulkadir, MohamedYu, DongmeiOsiecki, LisaKing, Robert A.Fernandez, Thomas V.Brown, Lawrence W.Mir Rivera, PabloHoekstra, Pieter J.2022-12-072022-12-072021-08-13Abdulkadir, M., Yu, D., Osiecki, L., King, R.A., Fernandez, T.V., Brown, L.W.,...,Hoekstra, P.J. (2021). Investigation of gene–environment interactions in relation to tic severit. Journal of Neural Transmission, 128 (11), 1757-1765. https://doi.org/10.1007/s00702-021-02396-y.0300-95641435-1463 (online)https://hdl.handle.net/11441/140213Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investi gated 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-defcit/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 efects of the SNPs on tic severity, and the interaction efect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of signifcance (after correcting for multiple testing) in a rep lication sample (N=678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was signifcantly related to higher tic severity. We found a gene–environment interaction for rs6539267, another top TS GWAS SNP. These fndings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene–environment studies.application/pdf9 p.engAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Gene–environment interactionPre- and perinatal complicationsTic severityTourette syndromeinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccesshttps://doi.org/10.1007/s00702-021-02396-y