Kong Ling-Li, Miao Dan, Tan Lin, Liu Shu-Lei, Li Jie-Qiong, Cao Xi-Peng, Tan Lan
Department of Geriatric Psychiatry, Qingdao Mental Health Center, Qingdao University, Qingdao 266071, China.
Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, China.
Ann Transl Med. 2018 Nov;6(22):436. doi: 10.21037/atm.2018.07.05.
Fluorodeoxyglucose f18 positron emission tomography (18F-FDG PET) is regarded as the only functional neuroimaging biomarker for degeneration which can be used to increase the certainty of Alzheimer's disease (AD) pathophysiological process in research settings or as an optional clinical tool where available. Although a decline in FDG metabolism was confirmed in some regions known to be associated with AD, there was little known about the genetic association of FDG metabolism in AD cohorts. In this study, we present the first genome-wide association study (GWAS) analysis of brain FDG metabolism.
A total of 222 individuals were included from the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) cohort. All subjects were restricted to non-Hispanic Caucasians and met all quality control (QC) criteria. Associations of 18F-FDG with the genetic variants were assessed using PLINK 1.07 under the additive genetic model. Genome-wide associations were visualized using a software program R 3.2.3.
One significant SNP rs12444565 in RNA-binding Fox1 () was found to have a strong association with 18F-FDG (P=6.06×10). Rs235141, rs79037, rs12526331 and rs12529764 were identified as four suggestive loci associated with 18F-FDG.
Our study results suggest that a genome-wide significant SNP (rs12444565) in the , and four suggestive loci (rs235141, rs79037, rs12526331 and rs12529764) are associated with 18F-FDG.
氟代脱氧葡萄糖F18正电子发射断层扫描（18F-FDG PET）被认为是唯一可用于增加研究环境中阿尔茨海默病（AD）病理生理过程确定性的功能性神经影像学生物标志物，或在可用时作为一种可选的临床工具。尽管在一些已知与AD相关的区域证实了FDG代谢下降，但关于AD队列中FDG代谢的遗传关联知之甚少。在本研究中，我们首次对脑FDG代谢进行了全基因组关联研究（GWAS）分析。
从阿尔茨海默病神经影像倡议1（ADNI-1）队列中纳入了总共222名个体。所有受试者均为非西班牙裔白种人，并符合所有质量控制（QC）标准。在加性遗传模型下，使用PLINK 1.07评估18F-FDG与基因变异的关联。使用软件程序R 3.2.3对全基因组关联进行可视化。
发现RNA结合蛋白Fox1（）中的一个显著单核苷酸多态性rs12444565与18F-FDG有强关联（P = 6.06×10）。Rs235141、rs79037、rs12526331和rs12529764被确定为与18F-FDG相关的四个提示性位点。
我们的研究结果表明，RNA结合蛋白Fox1中的一个全基因组显著单核苷酸多态性（rs12444565）以及四个提示性位点（rs235141、rs79037、rs12526331和rs12529764）与18F-FDG相关。
