Satizabal, CL;
Adams, HHH;
Hibar, DP;
White, CC;
Knol, MJ;
Stein, JL;
Scholz, M;
... Ikram, MA; + view all
(2019)
Genetic architecture of subcortical brain structures in 38,851 individuals.
Nature Genetics
, 51
(11)
pp. 1624-1636.
10.1038/s41588-019-0511-y.
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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.
| Type: | Article |
|---|---|
| Title: | Genetic architecture of subcortical brain structures in 38,851 individuals |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41588-019-0511-y |
| Publisher version: | https://doi.org/10.1038/s41588-019-0511-y |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, GENOME-WIDE ASSOCIATION, LD SCORE REGRESSION, BASAL GANGLIA, ALKALINE-PHOSPHATASE, ALZHEIMERS-DISEASE, PLASMA-PROTEIN, RISK LOCI, DROSOPHILA, METAANALYSIS, EXPRESSION |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10087531 |
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