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Genetic architecture of subcortical brain structures in 38,851 individuals

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journal contribution
posted on 20.04.2021, 13:10 authored by Claudia L Satizabal, Saud Alhusaini, Norman Delanty, Christopher Whelan, Gianpiero CavalleriGianpiero Cavalleri
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.


Details of funding agencies are on the paper.


Associated research data files

The genome-wide summary statistics that support the findings of this study are available from the CHARGE dbGaP (accession code: phs000930) and ENIGMA ( websites.


The original article is available at

Published Citation

Satizabal CL, et al. Genetic architecture of subcortical brain structures in 38,851 individuals. Nature Genetics. 2019;51(11):1624-1636.

Publication Date

21 October 2019

PubMed ID



  • Beaumont Hospital
  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Neurological and Psychiatric Disorders


Springer Nature Limited


  • Accepted Version (Postprint)