The relationship between four GWAS-identified loci in Alzheimer's disease and the risk of Parkinson's disease, amyotrophic lateral sclerosis, and multiple system atrophy
The relationship between four GWAS-identified loci in Alzheimer's disease and the risk of Parkinson's disease, amyotrophic lateral sclerosis, and multiple system atrophy
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GWAS 确定的四个阿尔茨海默病基因座与帕金森病、肌萎缩侧索硬化症和多系统萎缩风险之间的关系
DOI：
10.1016/j.neulet.2018.08.024
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发表时间：
2018-11-01
影响因子：
2.5
通讯作者：
Shang, Hui-Fang
中科院分区：
文献类型：
--
作者：
Chen, Yongping;Cao, Bei;Shang, Hui-Fang
背景：基于全基因组关联研究，先前已鉴定出许多遗传变异与阿尔茨海默病（AD）风险相关，包括 CELF1 中的 rs10838725、PTK2B 中的 rs28834970、FERMT2 中的 rs17125944 和 SIRT2 中的 rs10410544。考虑到AD与帕金森病（PD）、肌萎缩侧索硬化症（ALS）和多系统萎缩症（MSA）在临床表现和病理特征上的重叠，我们进行了大样本研究，探讨这些变异与中国人群中这三种常见神经退行性疾病之间的关联。方法：总共2449例患者，其中PD 1219例，散发性ALS 870例，MSA 360例，本研究对 821 名健康对照进行了检查。使用 Sequenom iPLEX 检测技术对所有病例进行单核苷酸多态性基因分型。结果：四种候选变异与三种神经退行性疾病之间的基因型分布和次要等位基因频率没有发现显着差异。然而，在认知功能正常和异常的PD患者之间，PTK2B中rs28834970的次要等位基因频率存在显着差异（p = 0.001）。此外，次要等位基因“C”与 PD 认知障碍风险增加相关（OR = 1.84）。尽管这一观察结果并不显着 (p = 0.064)，但具有 rs28834970 风险等位基因的 PD 患者的平均阿登布鲁克认知检查修订 (ACER) 评分比不具有风险等位基因的 PD 患者低 2.913 +/- 1.569 分。 结论：这项研究为可能具有不同神经退行性疾病共同发病机制的一些表型提供了新的见解。疾病。
Background: A number of genetic variants have previously been identified and associated with the risk of Alzheimer's disease (AD), including rs10838725 in CELF1, rs28834970 in PTK2B, rs17125944 in FERMT2, and rs10410544 in SIRT2 based on genome-wide association studies. Considering the overlap between the clinical manifestation and pathological characteristics of AD and Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA), we conducted a large sample study to investigate the associations between these variants and these three common neurodegenerative diseases in a Chinese population.Methods: A total of 2449 patients, including 1219 PD, 870 sporadic ALS, and 360 MSA, and 821 healthy controls were examined for this study. All cases were genotyped for single-nucleotide polymorphisms using Sequenom iPLEX assay technology.Results: No significant differences were found in genotype distribution and minor allele frequencies between the four candidate variants and the three neurodegenerative diseases. However, a significant difference was found in the minor allele frequency of rs28834970 in PTK2B between PD patients with normal and abnormal cognitive function (p = 0.001). Moreover, the minor allele "C" was associated with an increased risk for cognitive impairment in PD (OR = 1.84). Although this observation was not significant (p = 0.064), the mean Addenbrooke's Cognitive Examination-Revised (ACER) score of PD patients with the risk allele of rs28834970 was 2.913 +/- 1.569 points lower than that of PD patients without the risk allele.Conclusion: This study provides new insight into some of the phenotypes that may share the common pathogenesis of different neurodegenerative diseases.