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@ARTICLE{Federmann:1043713,
author = {Federmann, Lydia M. and Sindermann, Lisa and Primus,
Sabrina and Raimondo, Federico and Oexle, Konrad and
Goltermann, Janik and Winkelmann, Juliane and Nöthen,
Markus M. and Amunts, Katrin and Mühleisen, Thomas W. and
Cichon, Sven and Eickhoff, Simon B. and Hoffstaedter, Felix
and Dannlowski, Udo and Patil, Kaustubh R. and Forstner,
Andreas J.},
title = {{N}eurobiological correlates of schizophrenia-specific and
highly pleiotropic genetic risk scores for neuropsychiatric
disorders},
journal = {Translational Psychiatry},
volume = {15},
number = {1},
issn = {2158-3188},
address = {London},
publisher = {Nature Publishing Group},
reportid = {FZJ-2025-02999},
pages = {230},
year = {2025},
abstract = {Neuropsychiatric disorders show shared and distinct
neurobiological correlates. A cross-disorder genome-wide
association study (GWAS) identified 23 highly pleiotropic
single-nucleotide polymorphisms (SNPs) that were associated
with at least four neuropsychiatric disorders, and 22 SNPs
that were associated predominantly with schizophrenia.
Exploring their link to brain-related traits might advance
understanding their distinct neurobiological processes.
Using the UK Biobank data (n = 28,952), this study examined
the association of both a genetic risk score (GRS) for
highly pleiotropic SNPs (PleioPsych-GRS), and a GRS for
predominantly schizophrenia-associated SNPs (SCZ-GRS) with
154 measures of subcortical volume, cortical thickness, and
surface area as well as 12 outcomes related to mental
health. To generate further insights at the individual SNP
level, the association between SNPs and brain structure was
examined using GWAS summary statistics. The PleioPsych-GRS
showed no significant association with brain structure after
correction for multiple testing. The SCZ-GRS showed a
significant association with an increased surface area of
the lateral orbitofrontal region, and an increased volume of
the putamen, among others. The PleioPsych-GRS and the
SCZ-GRS were associated with eight and four outcomes related
to mental health, respectively. Two highly pleiotropic and
10 SCZ-associated SNPs were associated with several
structural brain phenotypes. Taken together, these findings
indicated that GRSs of highly pleiotropic SNPs and
predominantly schizophrenia-associated SNPs have partly
distinct associations with brain structure and outcomes
related to mental health. Thus, investigating
schizophrenia-specific and pleiotropic variants may improve
our understanding of the neurobiology of neuropsychiatric
disorders.},
cin = {INM-7 / INM-1},
ddc = {610},
cid = {I:(DE-Juel1)INM-7-20090406 / I:(DE-Juel1)INM-1-20090406},
pnm = {5251 - Multilevel Brain Organization and Variability
(POF4-525) / 5252 - Brain Dysfunction and Plasticity
(POF4-525)},
pid = {G:(DE-HGF)POF4-5251 / G:(DE-HGF)POF4-5252},
typ = {PUB:(DE-HGF)16},
pubmed = {40617812},
UT = {WOS:001522801400003},
doi = {10.1038/s41398-025-03440-1},
url = {https://juser.fz-juelich.de/record/1043713},
}