中老年人2型糖尿病遗传风险与脑灰质体积的关联研究

Study on the association between the genetic risk score for type 2 diabetes mellitus and brain gray matter volume in the middle-aged and elderly people

目的:探讨中老年人2型糖尿病(Type 2 diabetes mellitus,T2DM)遗传风险评分(Genetic risk score,GRS_(T2DM))与脑灰质体积(Gray matter volume,GMV)的相关性,并分析GRS_(T2DM)是否通过调控GMV进而影响记忆表现。方法:对116例中老年受试者(男54例,女62例,平均年龄(57.3±7.9)岁)进行高分辨率三维T_(1)加权成像(3D-T_(1)WI),采用基于体素的形态学(Voxelbased morphometry,VBM)方法获得全脑GMV图。使用三种方法(Simple count-GRS_(T2DM)(SC-GRS_(T2DM)),Odds ratio weighted-GRS_(T2DM)(OR-GRS_(T2DM)),Explained variance weighted-GRS_(T2DM)(EV-GRS_(T2DM)))分别计算每个受试者的GRS_(T2DM)。利用统计参数图软件(SPM12)进行基于体素的回归分析,探索GMV与GRS_(T2DM)相关的脑区,并通过中介效应分析评估GMV对GRS_(T2DM)和记忆表现之间的中介效应。结果:三种计算方法获得的中老年人GRS_(T2DM)均与右侧枕叶GMV呈显著负相关(AlphaSim校正,团块水平P<0.05),基于兴趣区的相关分析也显示GRS_(T2DM)与右侧枕叶GMV显著负相关(SC-GRS_(T2DM):r=-0.310,P=0.001;OR-GRS_(T2DM):r=-0.331,P<0.001;EV-GRS_(T2DM):r=-0.353,P<0.001)。右侧枕叶GMV介导了中老年人的GRS_(T2DM)和工作记忆之间的关联。结论:中老年人T2DM遗传风险与脑GMV相关,可能通过调控GMV进而影响记忆功能。

Objective:To investigate the association between the genetic risk score for type 2 diabetes mellitus(GRS_(T2DM))and brain gray matter volume(GMV)in the middle-aged and elderly people,and to evaluate whether GMV mediates the association between the GRS_(T2DM) and memory performance.Methods:High resolution three dimensions T_(1)-weighted imaging was collected from 116 middle-aged and elderly subjects(male 54,female 62,average age 57.3±7.9).Voxel-based morphology(VBM)method was used to calculate the GMV maps.The GRS_(T2DM) of all subjects were calculated with three different methods(Simple count-GRS_(T2DM)(SC-GRS_(T2DM)),odds ratio weighted-GRS_(T2DM)(OR-GRS_(T2DM)),explained variance weighted-GRS_(T2DM)(EVGRS_(T2DM))).Statistical parameter mapping software(SPM12)was used to perform a voxel-based regression analysis to explore the brain area in which the GMV was significantly associated with the GRS_(T2DM).Then the mediation effect of GMV on the association between the GRS_(T2DM) and memory performances was evaluated using mediation analysis.Results:The GRS_(T2DM) calculated with three methods were significantly negatively associated with the GMV of the right occipital lobe(AlphaSim correction,cluster level P<0.05).ROI-based correlation analysis further confirmed the associations between the GRS_(T2DM) and the GMV of the right occipital lobe(SC-GRS_(T2DM):r=-0.310,P=0.001;OR-GRS_(T2DM):r=-0.331,P<0.001;EV-GRS_(T2DM):r=-0.353,P<0.001).Mediation analysis showed that the GMV of the right occipital lobe might modulate the association between the GRS_(T2DM) and the working memory performance.Conclusion:The GRS_(T2DM) was significantly associated with the brain GMV in the middle-aged and elderly people,and might affect the memory function by modulating the GMV.