학술논문

Investigation of gene-environment interactions in relation to tic severity.
Document Type
article
Source
Journal of neural transmission (Vienna, Austria : 1996). 128(11)
Subject
Humans
Tourette Syndrome
Tics
Severity of Illness Index
Attention Deficit Disorder with Hyperactivity
Pregnancy
Female
Genome-Wide Association Study
Gene-Environment Interaction
Autism Spectrum Disorder
Gene–environment interaction
Pre- and perinatal complications
Tic severity
Tourette syndrome
Mental Health
Autism
Genetics
Pediatric
Neurosciences
Serious Mental Illness
Brain Disorders
Human Genome
Neurodegenerative
Intellectual and Developmental Disabilities (IDD)
Aetiology
2.1 Biological and endogenous factors
Mental health
Gene-environment interaction
Psychology
Neurology & Neurosurgery
Language
Abstract
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.