Investigation of gene–environment interactions in relation to tic severity

Mohamed Abdulkadir, Dongmei Yu, Lisa Osiecki, Robert A. King, Thomas V. Fernandez, Lawrence W. Brown, Keun Ah Cheon, Barbara J. Coffey, Blanca Garcia-Delgar, Donald L. Gilbert, Dorothy E. Grice, Julie Hagstrøm, Tammy Hedderly, Isobel Heyman, Hyun Ju Hong, Chaim Huyser, Laura Ibanez-Gomez, Young Key Kim, Young Shin Kim, Yun Joo KohSodahm Kook, Samuel Kuperman, Bennett Leventhal, Marcos Madruga-Garrido, Athanasios Maras, Pablo Mir, Astrid Morer, Alexander Münchau, Kerstin J. Plessen, Veit Roessner, Eun Young Shin, Dong Ho Song, Jungeun Song, Frank Visscher, Samuel H. Zinner, Carol A. Mathews, Jeremiah M. Scharf, Jay A. Tischfield, Gary A. Heiman, Andrea Dietrich, Pieter J. Hoekstra

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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.

Original languageEnglish
Pages (from-to)1757-1765
Number of pages9
JournalJournal of Neural Transmission
Issue number11
StatePublished - Nov 2021


  • Gene–environment interaction
  • Pre- and perinatal complications
  • Tic severity
  • Tourette syndrome


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