Genetic architecture of tic disorders: A systematic review of 125 observational studies

Background: To summarize and evaluate recent advances in the genetics of tic disorders (TDs) and to understand the possible pathogenic mechanisms behind this disorder. Methods: PubMed, EMBASE, the Cochrane Library, and four Chinese databases were searched from inception to September 2022. Observational original studies that explored genetic or chromosomal variations associated with the etiology, diagnosis, treatment, or prognosis of TDs were included. The Strengthening the Reporting of Genetic Association Studies (STREGA) statement was used to evaluate the quality of the included studies. Results: 125 studies were finally included with 119 of moderate quality and 6 of low quality. A total of 32,439 cases with different types of TDs and 81,923 controls were included. The results involved 98 genes, 16 chromosomes, and multiple gene sets. Genome-wide studies were also included. The top three systems were the dopamine system, nervous system development, and the serotonin system. 96 loci in 56 genes and 20 regions in 14 chromosomes were reported to be relevant to TDs, with SLC6A4 (serotonin system) and NTN4 genes being relatively strongly correlated with the occurrence of TS, and ACP1 (serotonin system) and DBH (dopamine system) being relatively strongly correlated with TS comorbid with attention deficit hyperactivity disorder (ADHD). Conclusion: Polygenic loci were found to play a key role in the occurrence and development of TDs. However, the applicability of the findings may be limited due to the small sample size, single-center design and the limited study quality of included studies. Future research with more comprehensive study designs and improved reporting transparency is needed to confirm the findings.