Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA.
Curr Alzheimer Res. 2012 Sep;9(7):801-14. doi: 10.2174/156720512802455331.
Copy number variants (CNVs) are DNA regions that have gains (duplications) or losses (deletions) of genetic material. CNVs may encompass a single gene or multiple genes and can affect their function. They are hypothesized to play an important role in certain diseases. We previously examined the role of CNVs in late-onset Alzheimer's disease (AD) and mild cognitive impairment (MCI) using participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study and identified gene regions overlapped by CNVs only in cases (AD and/or MCI) but not in controls. Using a similar approach as ADNI, we investigated the role of CNVs using 794 AD and 196 neurologically evaluated control non-Hispanic Caucasian NIA-LOAD/NCRAD Family Study participants with DNA derived from blood/brain tissue. The controls had no family history of AD and were unrelated to AD participants. CNV calls were generated and analyzed after detailed quality review. 711 AD cases and 171 controls who passed all quality thresholds were included in case/control association analyses, focusing on candidate gene and genome-wide approaches. We identified genes overlapped by CNV calls only in AD cases but not controls. A trend for lower CNV call rate was observed for deletions as well as duplications in cases compared to controls. Gene-based association analyses confirmed previous findings in the ADNI study (ATXN1, HLA-DPB1, RELN, DOPEY2, GSTT1, CHRFAM7A, ERBB4, NRXN1) and identified a new gene (IMMP2L) that may play a role in AD susceptibility. Replication in independent samples as well as further analyses of these gene regions is warranted.
拷贝数变异（CNVs）是指具有遗传物质获得（重复）或缺失（缺失）的 DNA 区域。CNVs 可以包含一个或多个基因，并可能影响其功能。它们被假设在某些疾病中发挥重要作用。我们之前使用阿尔茨海默病神经影像学倡议（ADNI）研究的参与者研究了 CNVs 在迟发性阿尔茨海默病（AD）和轻度认知障碍（MCI）中的作用，并确定了仅在病例（AD 和/或 MCI）中而不在对照中重叠的 CNV 基因区域。使用与 ADNI 类似的方法，我们使用来自血液/脑组织的 DNA 调查了 NIA-LOAD/NCRAD 家族研究的 794 名 AD 和 196 名神经学评估的非西班牙裔白种对照非 AD 参与者中的 CNV 作用。对照组没有 AD 家族史，与 AD 参与者无关。在经过详细质量审查后，生成和分析了 CNV 调用。通过所有质量阈值的 711 例 AD 病例和 171 例对照被纳入病例/对照关联分析，重点是候选基因和全基因组方法。我们确定了仅在 AD 病例中而不在对照中重叠的 CNV 调用基因。与对照组相比，病例中缺失和重复的 CNV 调用率呈下降趋势。基于基因的关联分析证实了 ADNI 研究中的先前发现（ATXN1、HLA-DPB1、RELN、DOPEY2、GSTT1、CHRFAM7A、ERBB4、NRXN1），并确定了一个可能在 AD 易感性中起作用的新基因（IMMP2L）。需要在独立样本中进行复制以及对这些基因区域进行进一步分析。
