Assessment of Candidate Loci in Neurological diseases

神经系统疾病候选基因座的评估

• 批准号: 7964116
• 负责人: Andrew Singleton
• 金额: $ 58.05万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7964116
• 关键词: Alzheimer' s Disease; Ataxia; Disease; Dystonia; Family; Genes; ITPR1 gene; Individual; LRRK2 gene; Molecular; Multiple System Atrophy; Mutation; Nature; Odds Ratio; Parkinson Disease; Primary Lateral Sclerosis; Process; Publishing; Risk Factors; SNCA gene; Screening procedure; Spinocerebellar Ataxias; Time; Work; genetic risk factor; insight; nervous system disorder; novel; proband; research study

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.

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。 我们通过筛查共济失调先证者中的TTBK 2和ITPR 1（我们早期发现这些基因的突变是共济失调的原因），扩展了我们在脊髓小脑共济失调方面的工作。 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。