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Genetic architecture of subcortical brain structures in 38,851 individuals

Research output: Contribution to journalArticlepeer-review

Claudia L. Satizabal, Hieab H.H. Adams, Derrek P. Hibar, Charles C. White, Maria J. Knol, Jason L. Stein, Markus Scholz, Muralidharan Sargurupremraj, Neda Jahanshad, Gennady V. Roshchupkin, Albert V. Smith, Joshua C. Bis, Xueqiu Jian, Michelle Luciano, Edith Hofer, Alexander Teumer, Sven J. van der Lee, Jingyun Yang, Lisa R. Yanek, Tom V. Lee & 30 more Shuo Li, Yanhui Hu, Jia Yu Koh, John D. Eicher, Sylvane Desrivières, Alejandro Arias-Vasquez, Ganesh Chauhan, Lavinia Athanasiu, Miguel E. Rentería, Sungeun Kim, David Hoehn, Nicola J. Armstrong, Qiang Chen, Avram J. Holmes, Anouk den Braber, Iwona Kloszewska, Micael Andersson, Thomas Espeseth, Oliver Grimm, Lucija Abramovic, Saud Alhusaini, Yuri Milaneschi, Martina Papmeyer, Tomas Axelsson, Saskia P. Hagenaars, Esther Walton, Tianye Jia, Christine Macare, Andrew Simmons, Gunter Schumann

Original languageEnglish
Pages (from-to)1624-1636
Number of pages13
JournalNature Genetics
Issue number11
Early online date21 Oct 2019
Accepted/In press5 Sep 2019
E-pub ahead of print21 Oct 2019
PublishedNov 2019


King's Authors


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.

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