Whole-exome Sequencing Identifies High-Confidence Genes for Tic Disorders in a Chinese Han Population

BACKGROUND:Tic disorder (TD) is a polygenic neurodevelopmental disorder with high susceptibility. However, identifying high-confidence risk genes has been challenging due to poor replication across multiple studies. METHODS:Whole-exome sequencing was performed on 390 TD patients and 372 unaffected individuals in a Chinese Han population. Analysis of variance, burden analysis and in silico prediction were used to identify candidate genes for TD. To facilitate data analysis and to focus on high-confidence genes, we defined a panel of 160 genes as known causal or candidate TD genes from previous studies. Gene enrichment and protein-protein interaction analysis were utilized to detect potential novel TD risk genes. RESULTS:Totally, 14 variants across 12 known TD candidate genes were considered potential susceptibility variants. Ten variants across 10 known TD candidate genes were identified as potential disease-causing variants. Burden analysis identified variants of 28 known genes were significantly excess in TD patients. In addition, 354 previously unproven TD genes are over-represented in patients. Genes enriched in the PI3K-Akt signaling, sphingolipid metabolism and serotonergic synaptic pathways, as well as those interacting with FN1, were considered potential new candidate genes for TD. CONCLUSIONS:This is the largest WES study focusing on TD patients in a Chinese Han population. Several variants recurring in our cohort were identified as high-confidence risk loci for TD. Moreover, we provided potential new risk genes that may be prioritized for further investigation.