Enhancing neuroimaging genetics through meta-analysis for Tourette syndrome (ENIGMA-TS): A worldwide platform for collaboration

Abstract

Tourette syndrome (TS) is characterized by multiple motor and vocal tics, and high-comorbidity rates with other neuropsychiatric disorders. Obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASDs), major depressive disorder (MDD), and anxiety disorders (AXDs) are among the most prevalent TS comorbidities. To date, studies on TS brain structure and function have been limited in size with efforts mostly fragmented. This leads to low-statistical power, discordant results due to differences in approaches, and hinders the ability to stratify patients according to clinical parameters and investigate comorbidity patterns. Here, we present the scientific premise, perspectives, and key goals that have motivated the establishment of the enhancing neuroimaging genetics through meta-analysis for TS (ENIGMA-TS). Working group ENIGMA-TS is an international collaborative effort bringing together a large network of investigators aiming to understand brain structure and function in TS and dissect the underlying neurobiology that leads to observed comorbidity patterns and clinical heterogeneity. Previously collected TS neuroimaging data will be analyzed jointly and integrated with genomic data, and also equivalently large and already existing studies of highly comorbid OCD, ADHD, ASD, MDD, and AXD. Our work highlights the power of collaborative efforts and transdiagnostic approaches, and points to the existence of different TS subtypes. ENIGMA-TS will offer large-scale, high-powered studies that will lead to important insights toward understanding brain structure and function and genetic effects in TS and related disorders, and also biomarkers that could help inform improved clinical practice.

Tourette-like syndrome secondary to Kleefstra syndrome 1 with a de novo microdeletion in the EHMT1 gene

“…The exact genetic mechanism underlying TS has yet to be fully understood. Still, it involves multiple genes that regulate neurotransmitters and synaptic plasticity [ 6 , 7 ]. Intriguingly, common TS comorbidities, including OCD, ADHD, and ASD, have been reported in KS1 patients, suggesting a shared genetic and neurobiological basis [ 8 – 10 ].…”

Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome

“…It is a childhood onset condition with a prevalence of 0.6 -0.8% in school age children and has a population heritability of 70% and SNP-based heritability estimates ranging from 0.21 to 0.58 [2][3][4][5][6] . TS is highly polygenic in nature and multiple genetic variants account for a substantial proportion of phenotypic variance of the condition [6][7][8][9][10][11] .…”