A Genomic and Bioinformatic Approach to Identify Genetic Variants for Tourette Syndrome

Abstract

Tourette syndrome (TS) is a neuropsychiatric disorder caused by damage to neurotransmitter metabolism in the brain, characterized by uncontrollable movements and vocals, also known as tics. The prevalence of Tourette syndrome is 0.6% in the global population, with a higher rate of 0.5% in the Americas, and predominantly impacting at a ratio of 4:1. The causes of Tourette syndrome can be genetic or non-genetic, with genetic factors often linked to mutations identified through Single Nucleotide Polymorphism (SNP). The study aims to identify specific gene variations associated with Tourette syndrome. The finding could serve as a preliminary step toward drug repurposing and the discovery of new treatments for Tourette syndrome. This study employs a design that integrates various databases, including the GWAS Catalog, HaploReg v4.2, the GTEx Portal, and Ensembl. The population in this study were all Single Nucleotide Polymorphism (SNP) data of Tourette syndrome disease from the GWAS Catalog, which amounted to 220 data. The samples in this study were Single Nucleotide Polymorphism (SNP) that met the inclusion criteria in the form of missense SNP with p-value < 5 x 10-8. The results revealed 115 SNPs with p-value < 5 x 10-8, of which only five were identified as missense mutations: rs13217619 (gene: ZSCAN12), rs4481150 (gene: ITIH3), rs2011503 (gene: SUGP1), rs7845911 (gene: DDHD2), and rs35225200 (gene: SLC39A8). The gene variation found in the five SNPs had the highest gene expression in the brain-cerebellum, thyroid, testis, prostate, and minor salivary gland tissues. The allele frequency distribution indicated that the SNP most closely associated with Tourette syndrome was found in the American continent (rs2011503) with a frequency of 88.2%. The test also showed the most significant impact on this SNP.