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Genetic architecture of subcortical brain structures in 38,854 individuals worldwide

MPG-Autoren
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Guadalupe,  Tulio
International Max Planck Research School for Language Sciences, MPI for Psycholinguistics, Max Planck Society;
Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society;

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Fisher,  Simon E.
Donders Institute for Brain, Cognition and Behaviour, External Organizations;
Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society;

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Francks,  Clyde
Donders Institute for Brain, Cognition and Behaviour, External Organizations;
Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society;
Imaging Genomics, MPI for Psycholinguistics, Max Planck Society;

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Zitation

Satizabal, C. L., Adams, H. H. H., Hibar, D. P., White, C. C., Knol, M. J., Stein, J. L., et al. (2019). Genetic architecture of subcortical brain structures in 38,854 individuals worldwide. Nature Genetics, 51, 1624-1636. doi:10.1038/s41588-019-0511-y.


Zitierlink: https://hdl.handle.net/21.11116/0000-0004-E358-9
Zusammenfassung
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.