Han Liting, Jiang Hanni, Yao Xufeng, Ren Zhe, Qu Zhongsen, Yu Tonggang, Luo Shichang, Wu Tao
College of Medical Imaging, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai, China.
College of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China.
Quant Imaging Med Surg. 2023 Apr 1;13(4):2451-2465. doi: 10.21037/qims-22-602. Epub 2023 Mar 22.
Alzheimer disease (AD) is a progressive neurodegenerative disease closely related to genes and characterized by the atrophy of the cerebral cortex. Correlations between imaging phenotypes and the susceptibility genes for AD, as demonstrated in the findings of genome-wide association studies (GWASs), still need to be addressed due to the complicated structure of the human cortex.
In our study, an improved GWAS method, whole cortex characteristics GWAS (WCC-GWAS), was proposed. The WCC-GWAS uses multiple cortex characteristics of gray-matter volume (GMV), cortical thickness (CT), cortical surface area (CSA), and local gyrification index (LGI). A cohort of 496 participants was enrolled and divided into 4 groups: normal control (NC; n=122), early mild cognitive impairment (EMCI; n=196), late mild cognitive impairment (LMCI; n=62), and AD (n=116). Based on the Desikan-Killiany atlas, the brain was parcellated into 68 brain regions, and the WCC of each brain region was individually calculated. Four cortex characteristics of GMV, CT, CSA, and LGI across the 4 groups optimized with multiple comparisons and the ReliefF algorithm were taken as magnetic resonance imaging (MRI) brain phenotypes. Under the model of multiple linear additive genetic regression, the correlations between the MRI brain phenotypes and single-nucleotide polymorphisms (SNPs) were deduced.
The findings identified 2 prominent correlations. First, rs7309929 of neuron navigator 3 () located on chromosome 12 correlated with the decreased GMV for the left middle temporal gyrus (P=0.0074). Second, rs11250992 of long intergenic non-protein-coding RNA 700 () located on chromosome 10 correlated with the decreased CT for the left supramarginal gyrus (P=0.0019).
The findings suggested that the correlations between phenotypes and genotypes could be effectively evaluated. The strategy of extracting MRI phenotypes as endophenotypes provided valuable indications in AD GWAS.
阿尔茨海默病（AD）是一种与基因密切相关的进行性神经退行性疾病，其特征为大脑皮质萎缩。由于人类皮质结构复杂，全基因组关联研究（GWAS）结果中所显示的成像表型与AD易感基因之间的相关性仍有待研究。
在我们的研究中，提出了一种改进的GWAS方法，即全皮质特征GWAS（WCC-GWAS）。WCC-GWAS使用灰质体积（GMV）、皮质厚度（CT）、皮质表面积（CSA）和局部脑回指数（LGI）等多种皮质特征。招募了496名参与者并将其分为4组：正常对照（NC；n = 122）、早期轻度认知障碍（EMCI；n = 196）、晚期轻度认知障碍（LMCI；n = 62）和AD（n = 116）。基于Desikan-Killiany图谱，将大脑划分为68个脑区，并分别计算每个脑区的WCC。采用多重比较和ReliefF算法优化后的4组GMV、CT、CSA和LGI这4种皮质特征作为磁共振成像（MRI）脑表型。在多重线性加性遗传回归模型下，推导MRI脑表型与单核苷酸多态性（SNP）之间的相关性。
研究结果确定了2个显著的相关性。第一，位于12号染色体上的神经导航蛋白3（）的rs7309929与左侧颞中回GMV降低相关（P = 0.0074）。第二，位于10号染色体上的长链基因间非编码RNA 700（）的rs11250992与左侧缘上回CT降低相关（P = 0.0019）。
研究结果表明，表型与基因型之间的相关性可以得到有效评估。提取MRI表型作为内表型的策略在AD的GWAS中提供了有价值的线索。
