Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, the Netherlands.
Hum Brain Mapp. 2021 Apr 15;42(6):1583-1593. doi: 10.1002/hbm.25292. Epub 2021 Feb 2.
Individual differences in subcortical brain volumes are highly heritable. Previous studies have identified genetic variants that underlie variation in subcortical volumes in adults. We tested whether those previously identified variants also affect subcortical regions during infancy and early childhood. The study was performed within the Generation R study, a prospective birth cohort. We calculated polygenic scores based on reported GWAS for volumes of the accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen, and thalamus. Participants underwent cranial ultrasound around 7 weeks of age (range: 3-20), and we obtained metrics for the gangliothalamic ovoid, a predecessor of the basal ganglia. Furthermore, the children participated in a magnetic resonance imaging (MRI) study around the age of 10 years (range: 9-12). A total of 340 children had complete data at both examinations. Polygenic scores primarily associated with their corresponding volumes at 10 years of age. The scores also moderately related to the diameter of the gangliothalamic ovoid on cranial ultrasound. Mediation analysis showed that the genetic influence on subcortical volumes at 10 years was only mediated for 16.5-17.6% of the total effect through the gangliothalamic ovoid diameter at 7 weeks of age. Combined, these findings suggest that previously identified genetic variants in adults are relevant for subcortical volumes during early life, and that they affect both prenatal and postnatal development of the subcortical regions.
大脑皮层下体积的个体差异具有高度遗传性。先前的研究已经确定了导致成年人大脑皮层下体积变化的遗传变异。我们测试了之前确定的变异是否也会影响婴儿期和幼儿期的大脑皮层下区域。这项研究是在“生育队列研究”（Generation R study）中进行的，这是一项前瞻性的出生队列研究。我们根据之前报道的大脑伏隔核、杏仁核、脑干、尾状核、苍白球、壳核和丘脑体积的全基因组关联研究（GWAS）计算了多基因分数。参与者在 7 周龄左右（范围：3-20 周）接受了颅超声检查，我们获得了神经节丘脑卵圆形的指标，这是基底节的前身。此外，这些儿童在 10 岁左右（范围：9-12 岁）参加了磁共振成像（MRI）研究。共有 340 名儿童在两次检查中均有完整的数据。多基因分数主要与 10 岁时的相应体积相关。这些分数与颅超声中神经节丘脑卵圆形的直径也有中度相关。中介分析表明，遗传对 10 岁时大脑皮层下体积的影响，只有通过 7 周龄时神经节丘脑卵圆形的直径来介导总效应的 16.5-17.6%。综合这些发现表明，先前在成年人中确定的遗传变异与生命早期的大脑皮层下体积有关，并且它们影响大脑皮层下区域的产前和产后发育。
