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基因对全脑和皮层下脑容量纵向变化个体差异的影响:ENIGMA可塑性工作组的结果

Genetic influences on individual differences in longitudinal changes in global and subcortical brain volumes: Results of the ENIGMA plasticity working group.

作者信息

Brouwer Rachel M, Panizzon Matthew S, Glahn David C, Hibar Derrek P, Hua Xue, Jahanshad Neda, Abramovic Lucija, de Zubicaray Greig I, Franz Carol E, Hansell Narelle K, Hickie Ian B, Koenis Marinka M G, Martin Nicholas G, Mather Karen A, McMahon Katie L, Schnack Hugo G, Strike Lachlan T, Swagerman Suzanne C, Thalamuthu Anbupalam, Wen Wei, Gilmore John H, Gogtay Nitin, Kahn René S, Sachdev Perminder S, Wright Margaret J, Boomsma Dorret I, Kremen William S, Thompson Paul M, Hulshoff Pol Hilleke E

机构信息

Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.

Department of Psychiatry, University of California, San Diego, California.

出版信息

Hum Brain Mapp. 2017 Sep;38(9):4444-4458. doi: 10.1002/hbm.23672. Epub 2017 Jun 5.

Abstract

Structural brain changes that occur during development and ageing are related to mental health and general cognitive functioning. Individuals differ in the extent to which their brain volumes change over time, but whether these differences can be attributed to differences in their genotypes has not been widely studied. Here we estimate heritability (h ) of changes in global and subcortical brain volumes in five longitudinal twin cohorts from across the world and in different stages of the lifespan (N = 861). Heritability estimates of brain changes were significant and ranged from 16% (caudate) to 42% (cerebellar gray matter) for all global and most subcortical volumes (with the exception of thalamus and pallidum). Heritability estimates of change rates were generally higher in adults than in children suggesting an increasing influence of genetic factors explaining individual differences in brain structural changes with age. In children, environmental influences in part explained individual differences in developmental changes in brain structure. Multivariate genetic modeling showed that genetic influences of change rates and baseline volume significantly overlapped for many structures. The genetic influences explaining individual differences in the change rate for cerebellum, cerebellar gray matter and lateral ventricles were independent of the genetic influences explaining differences in their baseline volumes. These results imply the existence of genetic variants that are specific for brain plasticity, rather than brain volume itself. Identifying these genes may increase our understanding of brain development and ageing and possibly have implications for diseases that are characterized by deviant developmental trajectories of brain structure. Hum Brain Mapp 38:4444-4458, 2017. © 2017 Wiley Periodicals, Inc.

摘要

在发育和衰老过程中发生的大脑结构变化与心理健康和一般认知功能有关。个体大脑体积随时间变化的程度存在差异,但这些差异是否可归因于基因型差异尚未得到广泛研究。在此,我们估计了来自世界各地、处于生命不同阶段的五个纵向双胞胎队列(N = 861)中全脑和皮质下脑体积变化的遗传力(h²)。对于所有全脑和大多数皮质下体积(丘脑和苍白球除外),大脑变化的遗传力估计值显著,范围从16%(尾状核)到42%(小脑灰质)。成人的变化率遗传力估计值通常高于儿童,这表明随着年龄增长,遗传因素对解释大脑结构变化个体差异的影响越来越大。在儿童中,环境影响在一定程度上解释了大脑结构发育变化的个体差异。多变量遗传模型显示,许多结构的变化率和基线体积的遗传影响显著重叠。解释小脑、小脑灰质和侧脑室变化率个体差异的遗传影响独立于解释其基线体积差异的遗传影响。这些结果意味着存在特定于大脑可塑性而非脑体积本身的遗传变异。识别这些基因可能会增进我们对大脑发育和衰老的理解,并可能对以大脑结构异常发育轨迹为特征的疾病产生影响。《人类大脑图谱》38:4444 - 4458,2017年。© 2017威利期刊公司。

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