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Genetic architecture of subcortical brain structures in 38,851 individuals

MPS-Authors
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Hoehn,  David
Max Planck Institute of Psychiatry, Max Planck Society;

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Mirza-Schreiber,  Nazanin
RG Statistical Genetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Puetz,  Benno
RG Statistical Genetics, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons80505

Saemann,  Philipp G.
Max Planck Institute of Psychiatry, Max Planck Society;

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Holsboer,  Florian
Max Planck Institute of Psychiatry, Max Planck Society;

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Mueller-Myhsok,  Bertram
RG Statistical Genetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Citation

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 38,851 individuals. NATURE GENETICS, 51(11), 1624-1636. doi:10.1038/s41588-019-0511-y.


Cite as: http://hdl.handle.net/21.11116/0000-0009-6567-2
Abstract
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.