Association analysis of SYT11, FGF20, GCH1 rare variants in Parkinson's disease

Threshold values for deleteriousness: CADD greater than 15; Polyphen2 greater than 0.86; SIFT less than 0.05 [Colour figure can be viewed at wileyonlinelibrary.com] The SYT11 protein, synaptotagmin-11, is a synaptotagmin isoform, which regulates membrane trafficking in synaptic transmission. 5 Genetic studies have reported that the mutations in the SYT11 gene were linked with PD and schizophrenia. 6,7 Previous studies have suggested that the variants in the nearby GBA gene drive the SYT11 GWAS association with PD. 8 However, after exclusion of all GBA variant carriers, Uladzislau Rudakou and colleagues found that the rs945006601 in the SYT11 gene remained statistically significant between PD patients and healthy controls. [...]the variant rs945006601 in the SYT11 gene linked with PD was independent of GBA variants. Tetrahydrobiopterin is a cofactor for tyrosine hydroxylase that is a rate-limiting enzyme for dopamine biosynthesis. [...]variants in the GCH1 gene could cause dopa-responsive dystonia. 12 Moreover, many genetic association studies have also identified GCH1 variants that increased the risk for PD. 13,14 In our cohort, we only found one nonsynonymous variant (c.C552T, p.R186C) that exists in eight Parkinson's disease patients and four healthy controls. [...]analysis of conservation across different species and prediction of pathogenesis all suggested that the p.R186C variant may contribute to the pathogenesis of PD. Taken together, our results indicated that the 10 variants in SYT11, FGF20, GCH1 genes may not be causative variants for PD in eastern China.