Polygenic effects on cortical size and ADHD converge on a mid-gestational progenitor-to-neuron transition programme

A study involving genetic and neuroimaging data from 59,283 individuals (adults, children, and neonates) identified genetic associations between ADHD, anxiety, depression, and cortical size. Analyses showed these associations are primarily driven by a common genetic factor for cortical size and ADHD. Genetically predicted reduced cortical size is causal for ADHD, not vice versa. Single-nucleus study of developing cortex revealed that although cortical size and ADHD are enriched in different cell types, they converge on genetic programmes active during the transition between proliferating progenitors and neurons. This programme peaks at mid-gestation in regions where progenitor amplification and neuronal migration occur. The findings identify a molecular mechanism of neurogenesis enriched for polygenic effects of both cortical size and ADHD.