Department of Psychiatry, University of California, San Diego, La Jolla, California; Twin Research Laboratory, Center for Behavioral Genomics, University of California, San Diego, La Jolla, California; Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, La Jolla, California.
Am J Med Genet B Neuropsychiatr Genet. 2013 Oct;162B(7):751-61. doi: 10.1002/ajmg.b.32162.
Understanding the genetics of neuropsychiatric disorders requires an understanding of the genetics of brain structure and function. The Vietnam Era Twin Study of Aging (VETSA) is a longitudinal behavioral genetic study focused on cognitive and brain aging. Here, we describe basic science work carried out within the VETSA MRI study that provides meaningful contributions toward the study of neuropsychiatric disorders. VETSA produced the first comprehensive assessment of the heritability of cortical and subcortical brain structure sizes, all within the same individuals. We showed that neocortical thickness and surface area are largely genetically distinct. With continuous neocortical thickness maps, we demonstrated regional specificity of genetic influences, and that genetic factors did not conform to traditional regions of interest (ROIs). However, there was some evidence for different genetic factors accounting for different types of cortex, and for genetic relationships across cortical regions corresponding to anatomical and functional connectivity and brain maturation patterns. With continuous neocortical surface area maps, we confirmed the anterior-posterior gradient of genetic influences on cortical area patterning demonstrated in animal models. Finally, we used twin methods to create the first map of cortical ROIs based entirely on genetically informative data. We conclude that these genetically based cortical phenotypes may be more appropriate for genetic studies than traditional ROIs based on structure or function. Our results also suggest that cortical volume-the product of thickness and surface area-is a problematic phenotype for genetic studies because two independent sets of genes may be obscured. Examples supporting the validity of these conclusions are provided.
理解神经精神疾病的遗传学需要了解大脑结构和功能的遗传学。越南时代双胞胎衰老研究(VETSA)是一项针对认知和大脑衰老的纵向行为遗传学研究。在这里,我们描述了在 VETSA MRI 研究中进行的基础科学工作,这些工作为神经精神疾病的研究做出了有意义的贡献。VETSA 首次全面评估了皮质和皮质下脑结构大小的遗传性,所有这些都在同一个体中进行。我们表明,新皮质的厚度和表面积在很大程度上是由遗传决定的。通过连续的新皮质厚度图,我们证明了遗传影响的区域特异性,并且遗传因素不符合传统的感兴趣区域(ROI)。但是,有一些证据表明,不同的遗传因素解释了不同类型的皮质,以及皮质区域之间的遗传关系与解剖学和功能连接以及大脑成熟模式相对应。通过连续的新皮质表面积图,我们证实了动物模型中遗传对皮质区域模式的前后梯度影响。最后,我们使用双胞胎方法创建了第一个完全基于遗传信息数据的皮质 ROI 图。我们得出的结论是,与基于结构或功能的传统 ROI 相比,这些基于遗传的皮质表型可能更适合遗传研究。我们的结果还表明,皮质体积-厚度和表面积的乘积-是遗传研究中的一个有问题的表型,因为两个独立的基因集可能会被掩盖。提供了支持这些结论有效性的示例。