Investigation of gene-environment interactions in relation to tic severity
Authors
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
Citation
JOURNAL OF NEURAL TRANSMISSION, Vol.128(11) : 1757-1765, 2021-11
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.