Edinburgh Imaging

23 Oct 19. Featured Paper

Genetic architecture of subcortical brain structures in 38,851 individuals.






Claudia L. Satizabal; Charles C. White;  Joanna M. Wardlaw;  Sarah E. Medland; Joshua M. Shulman; Paul M. Thompson; Sudha Seshadri; M. Arfan Ikram …


Subcortical brain structures are integral to motion, consciousness, emotions and learning.


We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE (Childhood Autism Risks from Genetics and the Environment) , ENIGMA ( Enhancing Neuro Imaging Genetics through Meta Analysis) and UK Biobank (Improving the health of future generations).


We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms.


Our findings uncover novel biology and potential drug targets underlying brain development and disease.