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@ARTICLE{Andlauer:891609,
author = {Andlauer, Till F. M. and Mühleisen, Thomas W. and
Hoffstaedter, Felix and Teumer, Alexander and Wittfeld,
Katharina and Teuber, Anja and Reinbold, Céline S. and
Grotegerd, Dominik and Bülow, Robin and Caspers, Svenja and
Dannlowski, Udo and Herms, Stefan and Hoffmann, Per and
Kircher, Tilo and Minnerup, Heike and Moebus, Susanne and
Nenadić, Igor and Teismann, Henning and Völker, Uwe and
Etkin, Amit and Berger, Klaus and Grabe, Hans J. and
Nöthen, Markus M. and Amunts, Katrin and Eickhoff, Simon B.
and Sämann, Philipp G. and Müller-Myhsok, Bertram and
Cichon, Sven},
title = {{G}enetic factors influencing a neurobiological substrate
for psychiatric disorders},
journal = {Translational Psychiatry},
volume = {11},
number = {1},
issn = {2158-3188},
address = {London},
publisher = {Nature Publishing Group},
reportid = {FZJ-2021-01620},
pages = {192},
year = {2021},
abstract = {A retrospective meta-analysis of magnetic resonance imaging
voxel-based morphometry studies proposed that reduced gray
matter volumes in the dorsal anterior cingulate and the left
and right anterior insular cortex-areas that constitute hub
nodes of the salience network-represent a common substrate
for major psychiatric disorders. Here, we investigated the
hypothesis that the common substrate serves as an
intermediate phenotype to detect genetic risk variants
relevant for psychiatric disease. To this end, after a data
reduction step, we conducted genome-wide association studies
of a combined common substrate measure in four
population-based cohorts (n = 2271), followed by
meta-analysis and replication in a fifth cohort (n = 865).
After correction for covariates, the heritability of the
common substrate was estimated at 0.50 (standard error
0.18). The top single-nucleotide polymorphism (SNP)
rs17076061 was associated with the common substrate at
genome-wide significance and replicated, explaining $1.2\%$
of the common substrate variance. This SNP mapped to a locus
on chromosome 5q35.2 harboring genes involved in neuronal
development and regeneration. In follow-up analyses,
rs17076061 was not robustly associated with psychiatric
disease, and no overlap was found between the broader
genetic architecture of the common substrate and genetic
risk for major depressive disorder, bipolar disorder, or
schizophrenia. In conclusion, our study identified that
common genetic variation indeed influences the common
substrate, but that these variants do not directly translate
to increased disease risk. Future studies should investigate
gene-by-environment interactions and employ functional
imaging to understand how salience network structure
translates to psychiatric disorder risk.},
cin = {INM-7 / INM-1},
ddc = {610},
cid = {I:(DE-Juel1)INM-7-20090406 / I:(DE-Juel1)INM-1-20090406},
pnm = {525 - Decoding Brain Organization and Dysfunction
(POF4-525) / HBP SGA2 - Human Brain Project Specific Grant
Agreement 2 (785907) / JL SMHB - Joint Lab Supercomputing
and Modeling for the Human Brain (JL SMHB-2021-2027)},
pid = {G:(DE-HGF)POF4-525 / G:(EU-Grant)785907 / G:(DE-Juel1)JL
SMHB-2021-2027},
typ = {PUB:(DE-HGF)16},
pubmed = {33782385},
UT = {WOS:000636309900005},
doi = {10.1038/s41398-021-01317-7},
url = {https://juser.fz-juelich.de/record/891609},
}