Abdulkadir, MohamedYu, DongmeiOsiecki, LisaKing, Robert AFernandez, Thomas VBrown, Lawrence WCheon, Keun-AhCoffey, Barbara JGarcia-Delgar, BlancaGilbert, Donald LGrice, Dorothy EHagstrøm, JulieHedderly, TammyHeyman, IsobelHong, Hyun JuHuyser, ChaimIbanez-Gomez, LauraKim, Young KeyKim, Young-ShinKoh, Yun-JooKook, SodahmKuperman, SamuelLeventhal, BennettMadruga-Garrido, MarcosMaras, AthanasiosMir, PabloMorer, AstridMünchau, AlexanderPlessen, Kerstin JRoessner, VeitShin, Eun-YoungSong, Dong-HoSong, JungeunVisscher, FrankZinner, Samuel HMathews, Carol AScharf, Jeremiah MTischfield, Jay AHeiman, Gary ADietrich, AndreaHoekstra, Pieter J2025-01-072025-01-072021-08-13https://hdl.handle.net/10668/27465Tourette 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Gene–environment interactionPre- and perinatal complicationsTic severityTourette syndromeAttention Deficit Disorder with HyperactivityAutism Spectrum DisorderFemaleGene-Environment InteractionGenome-Wide Association StudyHumansPregnancySeverity of Illness IndexTicsTourette Syndromeresearch article34389898open access10.1007/s00702-021-02396-y1435-1463PMC8536549https://link.springer.com/content/pdf/10.1007/s00702-021-02396-y.pdfhttps://pmc.ncbi.nlm.nih.gov/articles/PMC8536549/pdf