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Investigation of gene-environment interactions in relation to tic severity

Research output: Contribution to journalJournal articlepeer-review

  • 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 Koh
  • Sodahm 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
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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
JournalJournal of Neural Transmission
Issue number11
Pages (from-to)1757-1765
Number of pages9
Publication statusPublished - Nov 2021

    Research areas

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

ID: 67060417