中老年人结构相似网络与脑基因表达的关联研究  

A study on the correlation between morphometric similarity network and brain gene expression in the middle-aged and elderly people

作　　者：杜鑫[1] 刘巧慧 张扬[1] 王紫蕊 张权[1] DU Xin;LIU Qiao-hui;ZHANG Yang;WANG Zi-rui;ZHANG Quan(Department of Medical Imaging,General Hospital,Tianjin Medical University,Tianjin 300052,China)

机构地区：[1]天津医科大学总医院医学影像科,天津300052

出　　处：《天津医科大学学报》2023年第6期599-603,共5页Journal of Tianjin Medical University

基　　金：天津市自然科学基金多元投入基金项目面上项目(21JCYBJC01280);天津市自然科学基金重点项目(17JCZDJC36300);天津市教委科研计划(2022KJ241);天津市医学重点学科(专科)建设项目(TJYXZDXK-001A)。

摘　　要：目的:从全基因组脑表达的角度揭示人脑结构相似网络(MSN)的生物学基础。方法:基于194名正常中老年受试者[男88名,女106名,平均年龄(57.56±7.76岁)]的高分辨率三维T1加权成像(3D-T1WI)和弥散张量成像(DTI)数据,提取7个影像学特征指标,包括:皮层表面积、皮层厚度、灰质体积、高斯曲度、平均曲度、各向异性分数和平均扩散系数,构建MSN。同时借助艾伦人脑图谱(allen human brain atlas,AHBA)全基因组脑基因表达数据进行基因表达与MSN的空间关联分析。然后,对与MSN显著相关的基因进行富集分析。结果:所有连接密度阈值下194名受试者的平均MSN图与无阈值的MSN图均存在显著相关性(P_(autocorr)<0.05)。基因表达-MSN的空间关联分析发现了770个与中老年MSN显著相关的基因(bonferroni,P_(autocorr)<0.05),这些基因主要富集于突触信号转导和中枢神经系统发育等生物学过程,并且与自闭症、精神分裂症和重度抑郁等神经精神疾病的发生有关。其中,194名受试者的平均MSN与SLC26A4(r=0.619,P=3.311e-17)和SEMA4F(r=0.624,P=1.559e-16)的基因表达量呈正相关,与TRAPPC2B(r=-0.625,P=1.337e-17)和KCNA3(r=-0.617,P=4.349e-17)基因表达量呈负相关。结论:中老年人MSN受突触信号转导和中枢神经系统发育等通路基因的调控,是MSN用于神经精神疾病脑改变研究的生物学基础。Objective:To investigate the biological basis of human brain morphometric similarity network(MSN)from the perspective of whole genome brain expression.Methods:The MSN of seven features derived from images of high-resolution three-dimensional T1 weighted imaging(3D-T1WI)and diffusion tensor imaging(DTI),including cortical area,cortical thickness,gray matter volume,gaussian curvature,mean curvature,fractional anisotropy and mean diffusivity,acquired from the 194 middle-aged and elderly subjects[88 males and 106 females,average age(57.56±7.76)years]was calculated.Then,spatial association analysis of gene expression with MSN was conducted using the Allen Human Brain Atlas(AHBA)genome-wide brain gene expression data.Finally,enrichment analysis was performed on the gene list associated with MSN.Results:At all connection densities,there was a significant correlation between the mean MSN map of 194 subjects and the MSN map with no thresholding(P_(autocorr)<0.05).A total of 770 MSN-related genes significantly associated with middle-aged and elderly MSN were found by the spatial association analysis of gene expression MSN(bonferroni,P_(autocorr)<0.05),which were mainly enriched in biological process of the synaptic signaling and the central nervous system development etc.In additional,these genes were known to be involved in autistic disorder,schizophrenia,major depressive disorder and neurodevelopmental disorders etc.Among them,the mean MSN of 194 subjects was positively correlated with the gene expression of SLC26A4(r=0.619,P=3.311e-17)and SEMA4F(r=0.624,P=1.559e-16),while negatively correlated with the gene expression of TRAPPC2B(r=-0.625,P=1.337e-17)and KCNA3(r=-0.617,P=4.349e-17).Conclusion:MSN in middle-aged and elderly people is regulated by genes in the synaptic signal transduction and central nervous system development pathways,which is the biological basis of MSN used in the study of brain changes in neuropsychiatric diseases.

关 键 词：脑结构 磁共振成像 结构相似网络 基因表达 

分 类 号：R394[医药卫生—医学遗传学]