Assessment of Candidate Loci in Neurological diseases

在过去的一年中，我们发表了几项研究，确定了帕金森病中LRRK2，PRKN和PINK突变的程度和性质。这项工作的目的是进一步了解与这些基因突变相关的表型谱。 我们通过在共济失调先证者中筛选TTBK 2和ITPR 1来扩展我们在脊髓小脑共济失调中的工作（这些基因的突变被我们早期鉴定为共济失调的原因）。 值得注意的是，我们还在多系统萎缩（MSA）中进行了大型候选关联分析。这项工作首次表明，基因SNCA的常见变异是MSA的明确风险因素，比值比约为8。这为这种疾病提供了重要的病因学见解，以前没有发现遗传风险因素。

During the past year we have published several studies identifying the extent and nature of LRRK2, PRKN and PINK mutations in Parkinson's disease. This work aims to further our understanding of the phenotypic spectrum associated with mutation in these genes. We have extended our work in the spinocerebellar ataxias by screening of TTBK2 and ITPR1 in ataxia probands (mutations in these genes were identified earlier by us to be causes of ataxia). Notably we also performed a large candidate association analysis within multiple system atrophy (MSA). This work showed for the first time that common variability in the gene SNCA is an unequivocal risk factor for MSA with an odds ratio of approximately 8. This provides critical etiologic insight into this disorder, for which no genetic risk factor had previously been identified.