GWAS-Linked Loci and Neuroimaging Measures in Alzheimer's Disease
GWAS-Linked Loci and Neuroimaging Measures in Alzheimer's Disease
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DOI：
10.1007/s12035-015-9669-1
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发表时间：
2017-01-01
影响因子：
5.1
通讯作者：
Yu, Jin-Tai
中科院分区：
文献类型：
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作者：
Li, Jie-Qiong;Wang, Hui-Fu;Yu, Jin-Tai
最近，通过AD全基因组关联研究（GWAS）的荟萃分析，确定了19个阿尔茨海默病（AD）易感基因位点。然而，它们如何影响AD的发病机制仍然在很大程度上未知。我们在阿尔茨海默病神经影像学倡议（ADNI）数据库的一个大型队列中研究了具有六个MRI测量值、异常葡萄糖代谢和β-淀粉样蛋白（A β）沉积的神经影像学位点，以提供这些遗传变异可能起作用的机制的线索。因此，在随访研究中，MS 4A 6A内rs 983392和SOLR 1内rs 11218343处的单核苷酸多态性（SNP）均与左下颞区体积增加的百分比相关。同时，SORL 1位点rs 11218343和BIN 1位点rs6733839分别与左侧海马旁和右侧下顶叶的体积变化率相关。此外，CR 1处的rs6656401和MS 4A 6A处的rs 983392均与基线时右中颞叶体积较小相关。然而，除了APOE位点，我们没有检测到对葡萄糖代谢和A β沉积的任何影响。APOE等位基因与几乎所有指标相关。共检测到5个位点（CR 1的rs6656401、MS 4A 6A内的rs 983392、SORL 1的rs 11218343、BIN 1的rs6733839和APOE β 4）与一种或几种已确定的AD相关神经影像学指标相关。
Recently, 19 susceptibility loci for Alzheimer's disease (AD) had been identified through AD genome-wide association studies (GWAS) meta-analysis. However, how they influence the pathogenesis of AD still remains largely unknown. We studied those loci with six MRI measures, abnormal glucose metabolism, and beta-amyloid (A beta) deposition on neuroimaging in a large cohort from Alzheimer's Disease Neuroimaging Initiative (ADNI) database in order to provide clues of the mechanisms through which these genetic variants might be acting. As a result, single nucleotide polymorphisms (SNPs) at rs983392 within MS4A6A and rs11218343 within SOLR1 were both associated with the percentage of increase in the volume of left inferior temporal regions in the follow-up study. Meanwhile, rs11218343 at SORL1 and rs6733839 at BIN1 was associated with rate of volume change of left parahippocampal and right inferior parietal, respectively. Moreover, rs6656401 at CR1 and rs983392 at MS4A6A were both associated with smaller volume of right middle temporal at baseline. However, in addition to the APOE locus, we did not detect any influence on glucose metabolism and A beta deposition. APOE epsilon 4 allele was associated with almost all measures. Altogether, five loci (rs6656401 at CR1, rs983392within MS4A6A, rs11218343 at SORL1, rs6733839 at BIN1, and APOE epsilon 4) have been detected to be associated with one or a few established AD-related neuroimaging measures.