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人类脑形态变异的数量遗传建模。

Quantitative genetic modeling of variation in human brain morphology.

作者信息

Baaré W F, Hulshoff Pol H E, Boomsma D I, Posthuma D, de Geus E J, Schnack H G, van Haren N E, van Oel C J, Kahn R S

机构信息

Department of Psychiatry, University Medical Center Utrecht, the Netherlands.

出版信息

Cereb Cortex. 2001 Sep;11(9):816-24. doi: 10.1093/cercor/11.9.816.

Abstract

The degree to which individual variation in brain structure in humans is genetically or environmentally determined is as yet not well understood. We studied the brains of 54 monozygotic (33 male, 21 female) and 58 dizygotic (17 male, 20 female, 21 opposite sex) pairs of twins and 34 of their full siblings (19 male, 15 female) by means of high resolution magnetic resonance imaging scans. Structural equation modeling was used to quantify the genetic and environmental contributions to phenotypic (co)variance in whole brain, gray and white matter volume of the cerebrum, lateral ventricle volume and associated variables such as intracranial volume and height. Because the cerebral cortex makes up more that two-thirds of the brain mass and almost three-quarters of its synapses, our data predominantly concerns the telencephalon. Genetic factors accounted for most of the individual differences in whole brain (90%), gray (82%) and white (88%) matter volume. Individual differences in lateral ventricle volume were best explained by a model containing common (58%) and unique (42%) environmental factors, indicating genes to be of no or minor influence. In our sample, genetic or environmental influences were not different for males and females. The same genes influenced brain volumes and intracranial volume and almost completely explained their high phenotypic correlation. Genes influencing gray and white matter overlapped to a large extent and completely determined their phenotypic correlation. The high heritability estimates that were found indicate that brain volumes may be useful as intermediate phenotypes in behavioral genetic research.

摘要

人类大脑结构的个体差异在多大程度上由基因或环境决定,目前尚未完全明确。我们通过高分辨率磁共振成像扫描研究了54对同卵双胞胎(33名男性,21名女性)、58对异卵双胞胎(17名男性,20名女性,21对异性双胞胎)以及34名他们的同胞手足(19名男性,15名女性)的大脑。采用结构方程模型来量化基因和环境对全脑、大脑灰质和白质体积、侧脑室体积以及相关变量(如颅内体积和身高)的表型(协)方差的贡献。由于大脑皮层占大脑质量的三分之二以上,且其突触几乎占四分之三,因此我们的数据主要涉及端脑。基因因素占全脑(90%)、灰质(82%)和白质(88%)体积个体差异的大部分。包含共同(58%)和独特(42%)环境因素的模型能最好地解释侧脑室体积的个体差异,这表明基因影响不大或没有影响。在我们的样本中,男性和女性的基因或环境影响并无差异。相同的基因影响脑容量和颅内体积,几乎完全解释了它们之间高度的表型相关性。影响灰质和白质的基因在很大程度上重叠,并完全决定了它们的表型相关性。所发现的高遗传率估计表明,脑容量可能作为行为遗传学研究中的中间表型。

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