TY - JOUR
T1 - Genetic architecture of subcortical brain structures in 38,851 individuals
AU - ENIGMA
AU - Satizabal, Claudia L
AU - Adams, Hieab H H
AU - Hibar, Derrek P
AU - White, Charles C
AU - Knol, Maria J
AU - Stein, Jason L
AU - Scholz, Markus
AU - Sargurupremraj, Muralidharan
AU - Jahanshad, Neda
AU - Roshchupkin, Gennady V
AU - Smith, Albert V
AU - Bis, Joshua C
AU - Jian, Xueqiu
AU - Luciano, Michelle
AU - Hofer, Edith
AU - Teumer, Alexander
AU - van der Lee, Sven J
AU - Yang, Jingyun
AU - Yanek, Lisa R
AU - Lee, Tom V
AU - Li, Shuo
AU - Hu, Yanhui
AU - Koh, Jia Yu
AU - Eicher, John D
AU - Desrivières, Sylvane
AU - Arias-Vasquez, Alejandro
AU - Chauhan, Ganesh
AU - Athanasiu, Lavinia
AU - Rentería, Miguel E
AU - Kim, Sungeun
AU - Hoehn, David
AU - Armstrong, Nicola J
AU - Holmes, Avram J
AU - den Braber, Anouk
AU - Kloszewska, Iwona
AU - Andersson, Micael
AU - Espeseth, Thomas
AU - Grimm, Oliver
AU - Abramovic, Lucija
AU - Alhusaini, Saud
AU - Milaneschi, Yuri
AU - Papmeyer, Martina
AU - Axelsson, Tomas
AU - Ehrlich, Stefan
AU - Roiz-Santiañez, Roberto
AU - Kraemer, Bernd
AU - Håberg, Asta K
AU - Jones, Hannah J
AU - Pike, G Bruce
AU - Walton, Esther
PY - 2019/11/30
Y1 - 2019/11/30
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85074320860&partnerID=8YFLogxK
U2 - 10.1038/s41588-019-0511-y
DO - 10.1038/s41588-019-0511-y
M3 - Article
C2 - 31636452
SN - 1061-4036
VL - 51
SP - 1624
EP - 1636
JO - Nature Genetics
JF - Nature Genetics
IS - 11
ER -
