Cullen Harriet, Dimitrakopoulou Konstantina, Patel Hamel, Curtis Charles, Batalle Dafnis, Gale-Grant Oliver, Cordero-Grande Lucilio, Price Anthony, Hajnal Joseph V, Edwards A David
School of Biomedical Engineering and Imaging Sciences, Centre for the Developing Brain, King's College London, London, United Kingdom.
Department of Medical and Molecular Genetics, School of Basic and Medical Biosciences, King's College London, London, United Kingdom.
Front Neurosci. 2025 Jun 10;19:1546845. doi: 10.3389/fnins.2025.1546845. eCollection 2025.
Recent genome-wide association studies have identified numerous single nucleotide polymorphisms (SNPs) associated with subcortical brain volumes. These studies have been undertaken in largely adult cohorts. In this work we explore the role of common genetic variability in fetal and perinatal brain development. We investigate how genetic variation, known to be associated with adult subcortical brain volume, affects the infant subcortical brain.
We examine the influence of specific genetic loci and genome-wide polygenic scores on development of the fetal brain. Using a cohort of 208 term-born infants from the Developing Human Connectome Project, we ask whether eight SNPs, previously associated with adult subcortical brain volumes, show similar associations at birth. In addition, we compute genome-wide polygenic scores for the amygdala, brainstem, caudate, hippocampus, pallidum, putamen and thalamus and ask whether these scores are associated with the corresponding neonatal brain volumes.
We find that the association between SNP rs945270 and putamen volume, seen in adults, is present at birth ( = 3.67 × 10, β = 0.13, SE = 0.04). We also show that neonatal hippocampal, brainstem, putamen and thalamic volumes are all significantly associated with the genome-wide polygenic scores for their corresponding adult subcortical brain volume.
Our results suggest that common genetic variation, important in shaping adult subcortical brain volume, also plays a significant role in fetal and perinatal brain development.
最近的全基因组关联研究已经确定了许多与皮质下脑容量相关的单核苷酸多态性（SNP）。这些研究主要是在成年人群体中进行的。在这项工作中，我们探讨了常见基因变异在胎儿和围产期脑发育中的作用。我们研究了已知与成人大脑皮质下体积相关的基因变异如何影响婴儿的大脑皮质下结构。
我们研究了特定基因位点和全基因组多基因评分对胎儿脑发育的影响。利用来自人类连接组计划的208名足月出生婴儿的队列，我们询问先前与成人大脑皮质下体积相关的8个SNP在出生时是否显示出类似的关联。此外，我们计算了杏仁核、脑干、尾状核、海马体、苍白球、壳核和丘脑的全基因组多基因评分，并询问这些评分是否与相应的新生儿脑容量相关。
我们发现，在成年人中观察到的SNP rs945270与壳核体积之间的关联在出生时就存在（P = 3.67×10⁻³，β = 0.13，SE = 0.04）。我们还表明，新生儿海马体、脑干、壳核和丘脑的体积都与它们相应的成人大脑皮质下体积的全基因组多基因评分显著相关。
我们的结果表明，在塑造成人大脑皮质下体积方面起重要作用的常见基因变异，在胎儿和围产期脑发育中也起着重要作用。
