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000866305 0247_ $$2doi$$a10.1038/s41588-019-0511-y
000866305 0247_ $$2ISSN$$a1061-4036
000866305 0247_ $$2ISSN$$a1546-1718
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000866305 1001_ $$00000-0002-1115-4430$$aSatizabal, Claudia L.$$b0$$eCorresponding author
000866305 245__ $$aGenetic architecture of subcortical brain structures in 38,851 individuals
000866305 260__ $$aLondon$$bMacmillan Publishers Limited, part of Springer Nature$$c2019
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000866305 520__ $$aSubcortical 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.
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