NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
Mol Psychiatry. 2021 Aug;26(8):3876-3883. doi: 10.1038/s41380-020-0664-1. Epub 2020 Feb 11.
Sensitivity to external demands is essential for adaptation to dynamic environments, but comes at the cost of increased risk of adverse outcomes when facing poor environmental conditions. Here, we apply a novel methodology to perform genome-wide association analysis of mean and variance in ten key brain features (accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, intracranial volume, cortical surface area, and cortical thickness), integrating genetic and neuroanatomical data from a large lifespan sample (n = 25,575 individuals; 8-89 years, mean age 51.9 years). We identify genetic loci associated with phenotypic variability in thalamus volume and cortical thickness. The variance-controlling loci involved genes with a documented role in brain and mental health and were not associated with the mean anatomical volumes. This proof-of-principle of the hypothesis of a genetic regulation of brain volume variability contributes to establishing the genetic basis of phenotypic variance (i.e., heritability), allows identifying different degrees of brain robustness across individuals, and opens new research avenues in the search for mechanisms controlling brain and mental health.
对外部需求的敏感性对于适应动态环境至关重要，但当面临恶劣的环境条件时，会增加不良后果的风险。在这里，我们应用一种新的方法，对十个关键大脑特征（伏隔核、杏仁核、尾状核、海马体、苍白球、壳核、丘脑、颅内体积、皮质表面积和皮质厚度）的均值和方差进行全基因组关联分析，整合了来自大样本的遗传和神经解剖学数据（n=25575 人；8-89 岁，平均年龄 51.9 岁）。我们确定了与丘脑体积和皮质厚度表型可变性相关的遗传位点。控制方差的位点涉及到一些已被证明在大脑和精神健康方面发挥作用的基因，而这些基因与平均解剖体积无关。这一假说的初步验证，即遗传调控大脑体积可变性，有助于建立表型变异的遗传基础（即遗传力），可以识别个体之间大脑稳健性的不同程度，并为控制大脑和精神健康的机制研究开辟新的途径。
