Common Genetic Variation Important in Early Subcortical Brain Development


  1. Abstract 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. To better understand the role of genetic variability in foetal and perinatal brain development, we investigate how common genetic variation affects subcortical brain development in a cohort of 208 term-born infants from the Developing Human Connectome Project. We examine six SNPs, that have shown robust associations with subcortical brain volumes in adult studies and ask if these associations exist at birth. We then investigate whether genome-wide polygenic scores (GPSs) for adult subcortical brain volumes are predictive of the corresponding neonatal brain volume. Finally, we explore the relationship between GPSs for psychiatric disorders and subcortical brain volume at birth. We find the association between SNP rs945270 and putamen volume, seen in adults, is present at birth (p=3.67×10 -3 , β=0.13, SE=0.04). The associations between SNP rs61921502 and hippocampal volume and SNP rs11111090 and brainstem volume are also nominally present in our neonatal cohort. We show that neonatal hippocampal, brainstem, putamen and thalamic volume are all significantly associated with the GPSs for their corresponding volume in adults. Finally, we find that GPSs for five psychiatric disorders and a cross-disorder score are not significantly predictive of subcortical brain volumes or total brain volume at birth. Our results indicate that SNPs important in shaping adult subcortical brain volume are also significant in foetal and perinatal brain development. Key Points We show that the association between the single nucleotide polymorphism, rs945270 and putamen volume, seen in adults, is present in neonates. We show that neonatal hippocampal, putamen, brainstem and thalamic volumes are all significantly predicted by the genome-wide polygenic scores for corresponding adult brain volumes. We do not find any robust association between genome-wide polygenic scores for psychiatric disorders and neonatal brain volume although we observe several nominal associations.