Department of Biomedical Engineering, Hanyang University, Seoul, Korea.
Department of Radiology and Imaging Sciences, Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
Neurobiol Aging. 2021 Jun;102:200.e1-200.e11. doi: 10.1016/j.neurobiolaging.2021.01.021. Epub 2021 Feb 3.
To identify genetic variants influencing cortical atrophy in Alzheimer's disease (AD), we performed genome-wide association studies (GWAS) of mean cortical thicknesses in 17 AD-related brain. In this study, we used neuroimaging and genetic data of 919 participants from the Alzheimer's Disease Neuroimaging Initiative cohort, which include 268 cognitively normal controls, 488 mild cognitive impairment, 163 AD individuals. We performed GWAS with 3,041,429 single nucleotide polymorphisms (SNPs) for cortical thickness. The results of GWAS indicated that rs10109716 in ST18 (ST18 C2H2C-type zinc finger transcription factor) and rs661526 in NFIA (nuclear factor I A) genes are significantly associated with mean cortical thicknesses of the left inferior frontal gyrus and left parahippocampal gyrus, respectively. The rs661526 regulates the expression levels of NFIA in the substantia nigra and frontal cortex and rs10109716 regulates the expression levels of ST18 in the thalamus. These results suggest a crucial role of identified genes for cortical atrophy and could provide further insights into the genetic basis of AD.
为了鉴定影响阿尔茨海默病（AD）皮质萎缩的遗传变异，我们对 17 个与 AD 相关的大脑中的平均皮质厚度进行了全基因组关联研究（GWAS）。在这项研究中，我们使用了来自阿尔茨海默病神经影像学倡议队列的 919 名参与者的神经影像学和遗传数据，其中包括 268 名认知正常对照、488 名轻度认知障碍、163 名 AD 个体。我们对皮质厚度的 3041429 个单核苷酸多态性（SNP）进行了 GWAS。GWAS 的结果表明，ST18（ST18 C2H2C 型锌指转录因子）中的 rs10109716 和 NFIA（核因子 I A）基因中的 rs661526 分别与左侧额下回和左侧海马旁回的平均皮质厚度显著相关。rs661526 调节黑质和额叶皮质中 NFIA 的表达水平，rs10109716 调节丘脑 ST18 的表达水平。这些结果表明鉴定出的基因对皮质萎缩起着关键作用，并可能为 AD 的遗传基础提供进一步的见解。
