Yan Jingwen, Kim Sungeun, Nho Kwangsik, Chen Rui, Risacher Shannon L, Moore Jason H, Saykin Andrew J, Shen Li
BioHealth, Indiana University School of Informatics and Computing Indianapolis, IN, USA ; Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine Indianapolis, IN, USA.
Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine Indianapolis, IN, USA ; Indiana Alzheimer Disease Center, Indiana University School of Medicine Indianapolis, IN, USA.
Front Genet. 2015 Mar 26;6:117. doi: 10.3389/fgene.2015.00117. eCollection 2015.
As the most common type of dementia, Alzheimer's disease (AD) is a neurodegenerative disorder initially manifested by impaired memory performances. While the diagnosis information indicates a dichotomous status of a patient, memory scores have the potential to capture the continuous nature of the disease progression and may provide more insights into the underlying mechanism. In this work, we performed a targeted genetic study of memory scores on an AD cohort to identify the associations between a set of genes highly expressed in the hippocampal region and seven cognitive scores related to episodic memory. Both main effects and interaction effects of the targeted genetic markers on these correlated memory scores were examined. In addition to well-known AD genetic markers APOE and TOMM40, our analysis identified a new risk gene NAV2 through the gene-level main effect analysis. NAV2 was found to be significantly and consistently associated with all seven episodic memory scores. Genetic interaction analysis also yielded a few promising hits warranting further investigation, especially for the RAVLT list B Score.
作为最常见的痴呆类型，阿尔茨海默病（AD）是一种神经退行性疾病，最初表现为记忆功能受损。虽然诊断信息表明患者处于二分状态，但记忆分数有可能捕捉到疾病进展的连续性，并可能为潜在机制提供更多见解。在这项工作中，我们对一个AD队列进行了记忆分数的靶向基因研究，以确定一组在海马区高表达的基因与七个与情景记忆相关的认知分数之间的关联。研究了靶向基因标记对这些相关记忆分数的主效应和交互效应。除了众所周知的AD基因标记APOE和TOMM40外，我们的分析通过基因水平的主效应分析确定了一个新的风险基因NAV2。发现NAV2与所有七个情景记忆分数均存在显著且一致的关联。基因交互分析也产生了一些有前景的结果，值得进一步研究，特别是对于雷伊听觉词语学习测验（RAVLT）列表B分数。
