Genetic architecture of subcortical brain structures in 38,851 individuals.
Nat Genet. 2019-10-21; 51(11): 1624-1636
DOI: 10.1038/s41588-019-0511-y
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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, ENIGMA and UK Biobank. 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.