Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA.
Neuroimage. 2012 Apr 15;60(3):1686-95. doi: 10.1016/j.neuroimage.2012.01.122. Epub 2012 Feb 8.
The estimation of cortical thickness is in part dependent on the degree of contrast in T1 signal intensity between white matter and gray matter along the cortical mantle. The ratio of white matter to gray matter signal (WM/GM contrast) has been found to vary as a function of age and Alzheimer's disease status, suggesting a biological component to what might otherwise be labeled as a nuisance variable. The aim of the present study was to determine if measures of WM/GM contrast are genetically influenced, as well as the degree to which this phenotype may be related to the genetic and environment determinants of cortical thickness. Participants were 514 male twins (130 monozygotic, 97 dizygotic pairs, and 60 unpaired individuals) from the Vietnam Era Twin Study of Aging. Ages ranged from 51 to 59 years. Measures of WM/GM contrast and cortical thickness were derived for 66 cortical regions of interest (ROI) using FreeSurfer-based methods. Univariate and bivariate twin analyses were used in order to estimate the heritability of WM/GM contrast, as well as the degree of shared genetic and environmental variance between WM/GM contrast and cortical thickness. WM/GM contrast was found to be significantly heritable in the majority of ROIs. The average heritability across individual ROIs was highest in the occipital lobe (.50), and lowest in the cingulate cortex (.24). Significant phenotypic correlations between WM/GM contrast and cortical thickness were observed for most of the ROIs. The majority of the phenotypic correlations were negative, ranging from ?.11 to ?.54. Of the 66 associations, only 17 significant genetic correlations were found, ranging from ?.16 to ?.34, indicating small amounts of shared genetic variance. The majority of the phenotypic correlations were accounted for by small unique environmental effects common between WM/GM contrast and cortical thickness. These findings demonstrate that like cortical thickness, WM/GM contrast is a genetically influenced brain structure phenotype. The lack of significant genetic correlations with cortical thickness suggests that this measure potentially represents a unique source of genetic variance, one that has yet to be explored by the field of imaging genetics.
皮质厚度的估计部分取决于皮质层内白质和灰质之间 T1 信号强度的对比度。已经发现，白质与灰质信号的比值（WM/GM 对比度）随年龄和阿尔茨海默病状态而变化，这表明在某种程度上，这一指标可能受到生物学因素的影响，而不是被认为是一种干扰变量。本研究的目的是确定 WM/GM 对比度是否受到遗传因素的影响，以及这种表型与皮质厚度的遗传和环境决定因素的相关程度。参与者为来自越南时代老化双胞胎研究的 514 名男性双胞胎（130 对同卵双胞胎、97 对异卵双胞胎和 60 对非双胞胎），年龄在 51 岁至 59 岁之间。使用基于 FreeSurfer 的方法从 66 个感兴趣的皮质区域（ROI）中得出 WM/GM 对比度和皮质厚度的测量值。使用单变量和双变量双胞胎分析来估计 WM/GM 对比度的遗传率，以及 WM/GM 对比度和皮质厚度之间共享遗传和环境方差的程度。在大多数 ROI 中，WM/GM 对比度具有显著的遗传性。个体 ROI 之间的平均遗传率在枕叶最高（0.50），在扣带回最低（0.24）。在大多数 ROI 中，WM/GM 对比度与皮质厚度之间存在显著的表型相关性。这些表型相关性大多为负相关，范围从-0.11 到-0.54。在 66 个关联中，仅发现 17 个显著的遗传相关性，范围从 0.16 到 0.34，表明存在少量的共享遗传方差。大多数表型相关性是由 WM/GM 对比度和皮质厚度之间的小的独特环境效应共同造成的。这些发现表明，与皮质厚度一样，WM/GM 对比度是一种受遗传影响的大脑结构表型。与皮质厚度缺乏显著的遗传相关性表明，这种测量方法可能代表了一种独特的遗传变异来源，这一领域尚未被影像学遗传学领域所探索。
