CLU 和 PICALM 变体与阿尔茨海默病的关联。
Association of CLU and PICALM variants with Alzheimer's disease.
机构信息
Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA 15261, United States.
出版信息
Neurobiol Aging. 2012 Mar;33(3):518-21. doi: 10.1016/j.neurobiolaging.2010.04.015. Epub 2010 Jun 8.
Abstract
Two recent large genome-wide association studies have reported significant associations in the CLU (APOJ), CR1, and PICALM genes with the risk of Alzheimer's disease (AD). In order to replicate these findings, we examined 7 single nucleotide polymorphisms (SNPs) most significantly implicated by these studies in a large case-control sample comprising 2707 individuals. Principle components analysis revealed no population substructure in our sample. While no association was observed with CR1 SNPs (p = 0.30-0.457), a trend of association was seen with the PICALM (p = 0.071-0.086) and CLU (p = 0.148-0.258) SNPs. A meta-analysis of 3 studies revealed significant associations with all 3 genes. Our data from an independent and large case-control sample suggest that these gene regions should be followed up by comprehensive resequencing to find functional variants.
摘要
两项最近的全基因组关联研究报告称，CLU（APOJ）、CR1 和 PICALM 基因与阿尔茨海默病（AD）的风险显著相关。为了复制这些发现，我们在一个包含 2707 人的大型病例对照样本中，对这些研究中最显著关联的 7 个单核苷酸多态性（SNP）进行了检测。主成分分析显示，我们的样本中没有群体亚结构。虽然与 CR1 SNP 无关联（p = 0.30-0.457），但与 PICALM（p = 0.071-0.086）和 CLU（p = 0.148-0.258）SNP 呈关联趋势。3 项研究的荟萃分析显示与这 3 个基因均存在显著关联。我们来自独立且大型病例对照样本的数据表明，应通过全面重测序来跟进这些基因区域，以寻找功能变体。
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