CR1、CLU 和 PICALM 与临床特征明确且神经病理学验证的个体队列中的阿尔茨海默病的关联。
Association of CR1, CLU and PICALM with Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals.
机构信息
Neurogenomics Division, The Translational Genomics Research Institute (Gen, 445 N Fifth Street, Phoenix, AZ 85004, USA.
出版信息
Hum Mol Genet. 2010 Aug 15;19(16):3295-301. doi: 10.1093/hmg/ddq221. Epub 2010 Jun 9.
Abstract
In this study, we assess 34 of the most replicated genetic associations for Alzheimer's disease (AD) using data generated on Affymetrix SNP 6.0 arrays and imputed at over 5.7 million markers from a unique cohort of over 1600 neuropathologically defined AD cases and controls (1019 cases and 591 controls). Testing the top genes from the AlzGene meta-analysis, we confirm the well-known association with APOE single nucleotide polymorphisms (SNPs), the CLU, PICALM and CR1 SNPs recently implicated in unusually large data sets, and previously implicated CST3 and ACE SNPs. In the cases of CLU, PICALM and CR1, as well as in APOE, the odds ratios we find are slightly larger than those previously reported in clinical samples, consistent with what we believe to be more accurate classification of disease in the clinically characterized and neuropathologically confirmed AD cases and controls.
摘要
在这项研究中，我们使用来自一个独特的超过 1600 例神经病理学定义的 AD 病例和对照（1019 例病例和 591 例对照）的超过 570 万个标记物的 Affymetrix SNP 6.0 阵列生成的数据，并在超过 570 万个标记物上进行了推断，评估了 34 个最复制的阿尔茨海默病（AD）遗传关联。通过测试 AlzGene 荟萃分析中的顶级基因，我们证实了众所周知的 APOE 单核苷酸多态性（SNP）的关联，CLU、PICALM 和 CR1 SNP 最近在异常大的数据集以及先前涉及 CST3 和 ACE SNP 中被牵连。在 CLU、PICALM 和 CR1 以及 APOE 的情况下，我们发现的优势比与之前在临床样本中报告的稍大，这与我们认为在临床特征和神经病理学证实的 AD 病例和对照中对疾病的分类更准确一致。
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