Abstract
Recently, a genome-wide association study has indicated associations between single nucleotide polymorphisms in the Collagen Type XXVII Alpha 1 gene (COL27A1) and Tourette syndrome in several ethnic populations. To clarify the global relevance of the previously identified SNPs in the development of Tourette syndrome, the associations between polymorphisms in COL27A1and Tourette syndrome were assessed in Chinese trios. PCR-directed sequencing was used to evaluate the genetic contributions of three SNPs in COL27A1(rs4979356, rs4979357 and rs7868992) using haplotype relative risk (HRR) and transmission disequilibrium tests (TDT) with a total of 260 Tourette syndrome trios. The family-based association was significant between Tourette syndrome and rs4979356 (TDT: χ2 = 4.804, P = 0.033; HRR = 1.75, P = 0.002; HHRR = 1.32, P = 0.027), and transmission disequilibrium was suspected for rs4979357 (TDT: χ2 = 3.969, P = 0.053; HRR = 1.84, P = 0.001; HHRR = 1.29, P = 0.044). No statistically significant allele transfer was found for rs7868992 (TDT: χ2 = 2.177, P = 0.158). Although the TDT results did not remain significant after applying the conservative Bonferroni correction (p = 0.005), the significant positive HRR analysis confirmed the possibility of showing transmission disequilibrium, which provides evidence for an involvement of COL27A1in the development of TS. However, these results need to be verified with larger datasets from different populations.
Highlights
For the existence of a genetic background associated with a multifactorial mode of inheritance[5,6], and numerous studies aiming to explore genetic susceptibility of Tourette syndrome (TS) have been published[7,8,9,10]
The linkage disequilibrium (LD) analysis revealed that the 3 SNPs seems not in LD (D′ 1&2 = 0.538, D′ 1&3 = 0.541, D′ 2&3 = 0.586; r21&2 = 0.275, r21&3 = 0.222, r22&3 = 0 .248), meaning that the 3 SNPs were inherited independently
The transmission disequilibrium tests (TDT)-haplotype relative risk (HRR) results showed significant transmission disequilibrium for rs4979356 allele and genotype frequency (TDT = 4.804, df = 1, P = 0.033; HRR = 1.75, χ2 = 9.19, P = 0 .002, 95% CI: 1.2172.523)
Summary
For the existence of a genetic background associated with a multifactorial mode of inheritance[5,6], and numerous studies aiming to explore genetic susceptibility of TS have been published[7,8,9,10]. The genome-wide association study (GWAS) approach has led to the identification of many genetic associations for common complex traits[11] This model-free approach to gene discovery has led to a greater pathophysiological understanding of many disorders and can improve pharmaco-therapeutic strategies[12]. Scharf and colleagues performed the first GWAS of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel and French Canadians from Quebec, Canada. They found the strongest association was with rs7868992, which is within the Collagen Type XXVII Alpha 1 gene (COL27A1), (P = 1.85 × 10−6) in European-derived samples[13]. The objective of this study was to assess the genetic association of three SNPs in COL27A1 (rs4979356, rs4979357 and rs7868992) with TS in a Chinese Han population
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
