Chiang Ming-Chang, Barysheva Marina, Shattuck David W, Lee Agatha D, Madsen Sarah K, Avedissian Christina, Klunder Andrea D, Toga Arthur W, McMahon Katie L, de Zubicaray Greig I, Wright Margaret J, Srivastava Anuj, Balov Nikolay, Thompson Paul M
Laboratory of Neuro Imaging, Department of Neurology, University of California, Los Angeles, School of Medicine, Los Angeles, California 90095-7334, USA.
J Neurosci. 2009 Feb 18;29(7):2212-24. doi: 10.1523/JNEUROSCI.4184-08.2009.
The study is the first to analyze genetic and environmental factors that affect brain fiber architecture and its genetic linkage with cognitive function. We assessed white matter integrity voxelwise using diffusion tensor imaging at high magnetic field (4 Tesla), in 92 identical and fraternal twins. White matter integrity, quantified using fractional anisotropy (FA), was used to fit structural equation models (SEM) at each point in the brain, generating three-dimensional maps of heritability. We visualized the anatomical profile of correlations between white matter integrity and full-scale, verbal, and performance intelligence quotients (FIQ, VIQ, and PIQ). White matter integrity (FA) was under strong genetic control and was highly heritable in bilateral frontal (a(2)=0.55, p=0.04, left; a(2)=0.74, p=0.006, right), bilateral parietal (a(2)=0.85, p<0.001, left; a(2)=0.84, p<0.001, right), and left occipital (a(2)=0.76, p=0.003) lobes, and was correlated with FIQ and PIQ in the cingulum, optic radiations, superior fronto-occipital fasciculus, internal capsule, callosal isthmus, and the corona radiata (p=0.04 for FIQ and p=0.01 for PIQ, corrected for multiple comparisons). In a cross-trait mapping approach, common genetic factors mediated the correlation between IQ and white matter integrity, suggesting a common physiological mechanism for both, and common genetic determination. These genetic brain maps reveal heritable aspects of white matter integrity and should expedite the discovery of single-nucleotide polymorphisms affecting fiber connectivity and cognition.
该研究首次分析了影响脑纤维结构的遗传和环境因素及其与认知功能的遗传联系。我们在92对同卵和异卵双胞胎中,使用高磁场(4特斯拉)下的扩散张量成像逐体素评估白质完整性。使用分数各向异性(FA)量化的白质完整性,用于拟合大脑每个点的结构方程模型(SEM),生成遗传力的三维图谱。我们可视化了白质完整性与全量表、言语和操作智商(FIQ、VIQ和PIQ)之间相关性的解剖学概况。白质完整性(FA)受强大的遗传控制,在双侧额叶(左侧:a(2)=0.55,p=0.04;右侧:a(2)=0.74,p=0.006)、双侧顶叶(左侧:a(2)=0.85,p<0.001;右侧:a(2)=0.84,p<0.001)和左侧枕叶(a(2)=0.76,p=0.003)高度可遗传,并且在扣带、视辐射、额枕上束、内囊、胼胝体峡部和放射冠中与FIQ和PIQ相关(FIQ的p=0.04,PIQ的p=0.01,经多重比较校正)。在跨性状映射方法中,共同的遗传因素介导了智商与白质完整性之间的相关性,表明两者存在共同的生理机制和共同的遗传决定因素。这些遗传脑图谱揭示了白质完整性的可遗传方面,应能加快发现影响纤维连接性和认知的单核苷酸多态性。