Eyler Lisa T, Chen Chi-Hua, Panizzon Matthew S, Fennema-Notestine Christine, Neale Michael C, Jak Amy, Jernigan Terry L, Fischl Bruce, Franz Carol E, Lyons Michael J, Grant Michael, Prom-Wormley Elizabeth, Seidman Larry J, Tsuang Ming T, Fiecas Mark Joseph A, Dale Anders M, Kremen William S
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Twin Res Hum Genet. 2012 Jun;15(3):304-14. doi: 10.1017/thg.2012.3.
Understanding the genetic and environmental contributions to measures of brain structure such as surface area and cortical thickness is important for a better understanding of the nature of brain-behavior relationships and changes due to development or disease. Continuous spatial maps of genetic influences on these structural features can contribute to our understanding of regional patterns of heritability, since it remains to be seen whether genetic contributions to brain structure respect the boundaries of any traditional parcellation approaches. Using data from magnetic resonance imaging scans collected on a large sample of monozygotic and dizygotic twins in the Vietnam Era Twin Study of Aging, we created maps of the heritability of areal expansion (a vertex-based area measure) and cortical thickness and examined the degree to which these maps were affected by adjustment for total surface area and mean cortical thickness. We also compared the approach of estimating regional heritability based on the average heritability of vertices within the region to the more traditional region-of-interest (ROI)-based approach. The results suggested high heritability across the cortex for areal expansion and, to a slightly lesser degree, for cortical thickness. There was a great deal of genetic overlap between global and regional measures for surface area, so maps of region-specific genetic influences on surface area revealed more modest heritabilities. There was greater inter-regional variability in heritabilities when calculated using the traditional ROI-based approach compared to summarizing vertex-by-vertex heritabilities within regions. Discrepancies between the approaches were greatest in small regions and tended to be larger for surface area than for cortical thickness measures. Implications regarding brain phenotypes for future genetic association studies are discussed.
了解基因和环境对脑结构测量指标(如表面积和皮质厚度)的影响,对于更好地理解脑-行为关系的本质以及发育或疾病引起的变化至关重要。关于这些结构特征的基因影响的连续空间图谱,有助于我们理解遗传力的区域模式,因为基因对脑结构的贡献是否遵循任何传统分割方法的边界仍有待观察。利用越南战争时期双胞胎衰老研究中对大量同卵和异卵双胞胎进行磁共振成像扫描收集的数据,我们创建了面积扩张(基于顶点的面积测量)和皮质厚度的遗传力图谱,并研究了这些图谱受总表面积和平均皮质厚度调整影响的程度。我们还将基于区域内顶点平均遗传力估计区域遗传力的方法与更传统的基于感兴趣区域(ROI)的方法进行了比较。结果表明,皮质区域的面积扩张具有较高的遗传力,皮质厚度的遗传力略低。表面积的全局和区域测量之间存在大量遗传重叠,因此特定区域对表面积的基因影响图谱显示出较低的遗传力。与汇总区域内逐个顶点的遗传力相比,使用传统的基于ROI的方法计算时,遗传力的区域间变异性更大。两种方法之间的差异在小区域最为明显,并且对于表面积测量往往比对皮质厚度测量更大。文中讨论了对未来基因关联研究的脑表型的影响。