阿尔茨海默病语言能力的全基因组关联研究。
Genome-wide association study of language performance in Alzheimer's disease.
作者信息
Deters Kacie D, Nho Kwangsik, Risacher Shannon L, Kim Sungeun, Ramanan Vijay K, Crane Paul K, Apostolova Liana G, Saykin Andrew J
机构信息
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; Program in Medical Neuroscience, Paul and Carole Stark Neurosciences Research Institute, 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.
出版信息
Brain Lang. 2017 Sep;172:22-29. doi: 10.1016/j.bandl.2017.04.008. Epub 2017 May 31.
Language impairment is common in prodromal stages of Alzheimer's disease (AD) and progresses over time. However, the genetic architecture underlying language performance is poorly understood. To identify novel genetic variants associated with language performance, we analyzed brain MRI and performed a genome-wide association study (GWAS) using a composite measure of language performance from the Alzheimer's Disease Neuroimaging Initiative (ADNI; n=1560). The language composite score was associated with brain atrophy on MRI in language and semantic areas. GWAS identified GLI3 (GLI family zinc finger 3) as significantly associated with language performance (p<5×10). Enrichment of GWAS association was identified in pathways related to nervous system development and glutamate receptor function and trafficking. Our results, which warrant further investigation in independent and larger cohorts, implicate GLI3, a developmental transcription factor involved in patterning brain structures, as a putative gene associated with language dysfunction in AD.
语言障碍在阿尔茨海默病（AD）的前驱期很常见，且会随着时间推移而进展。然而，语言表现背后的遗传结构却知之甚少。为了识别与语言表现相关的新基因变异，我们分析了脑部磁共振成像（MRI），并使用来自阿尔茨海默病神经影像倡议（ADNI；n = 1560）的语言表现综合指标进行了全基因组关联研究（GWAS）。语言综合评分与语言和语义区域MRI上的脑萎缩相关。GWAS确定GLI3（GLI家族锌指蛋白3）与语言表现显著相关（p < 5×10）。在与神经系统发育以及谷氨酸受体功能和运输相关的通路中发现了GWAS关联的富集。我们的结果表明，GLI3作为一种参与脑结构模式形成的发育转录因子，是AD中与语言功能障碍相关的一个假定基因，这一结果值得在独立的更大队列中进一步研究。
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