Nat. Genet：帕金森氏病6个新的遗传危险因素
作者：admin 时间：2014-07-31 点击数：
2014年7月30日讯 /生物谷BIOON/--近日，科学家们新近确定参与帕金森病的二十几个遗传危险因素，包括以前没有被报道过的六个遗传因素。这项研究发表在Nature Genetics杂志上。
揭开帕金森的遗传基础对于了解这一复杂疾病的多种机制，以及找到有效的治疗方法是至关重要的。Andrew Singleton博士和他的同事们收集和综合现有的全基因组关联研究（GWAS）数据，试图找到患者的基因变异或细微的基因差别。收集到的数据来自约13,708帕金森氏症病例和95,282对照者，所有人均为欧洲血统。
研究者发现了增加患帕金森氏症几率的潜在遗传变异风险。他们的结果表明，一个人的变异越多，患病风险就更大，在某些情况下，患这种疾病的风险高达3倍。虽然9个基因变异已被证明可导致罕见形式的帕金森氏病，但科学家继续寻找遗传危险因素，以获得疾病一个完整的基因信息。
研究人员在另一样本中（包括5,353例患者和5,551例对照）证实了上述结果。研究人员证实了帕金森氏病的24个遗传危险因素，包括以前尚未被确定的六个变异。
一些新发现的遗传危险因素被认为参与Gaucher's病，调节炎症和神经细胞化学信使多巴胺以及α-突触核蛋白（α-突触核蛋白在某些帕金森氏病患者大脑中会聚集）。但还需要进一步研究，以确定在本研究中所发现的基因变异的作用。（生物谷Bioon.com）
Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease
Nalls et al.
We conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as having genome-wide significant association; these and 6 additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 newly identified loci. Conditional analyses within loci showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain a secondary independent risk variant. In total, we identified and replicated 28 independent risk variants for Parkinson's disease across 24 loci. Although the effect of each individual locus was small, risk profile analysis showed substantial cumulative risk in a comparison of the highest and lowest quintiles of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55–4.30; P = 2 × 10?16). We also show six risk loci associated with proximal gene expression or DNA methylation.
