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@ARTICLE{Thalamuthu:903474,
author = {Thalamuthu, Anbupalam and Mills, Natalie T. and Berger,
Klaus and Minnerup, Heike and Grotegerd, Dominik and
Dannlowski, Udo and Meinert, Susanne and Opel, Nils and
Repple, Jonathan and Gruber, Marius and Nenadić, Igor and
Stein, Frederike and Brosch, Katharina and Meller, Tina and
Pfarr, Julia-Katharina and Forstner, Andreas J. and
Hoffmann, Per and Nöthen, Markus M. and Witt, Stephanie and
Rietschel, Marcella and Kircher, Tilo and Adams, Mark and
McIntosh, Andrew M. and Porteous, David J. and Deary, Ian J.
and Hayward, Caroline and Campbell, Archie and Grabe, Hans
Jörgen and Teumer, Alexander and Homuth, Georg and van der
Auwera-Palitschka, Sandra and Oliver Schubert, K. and Baune,
Bernhard T.},
title = {{G}enome-wide interaction study with major depression
identifies novel variants associated with cognitive
function},
journal = {Molecular psychiatry},
volume = {27},
issn = {1359-4184},
address = {London},
publisher = {Macmillan},
reportid = {FZJ-2021-05146},
pages = {1111–1119},
year = {2022},
abstract = {Major Depressive Disorder (MDD) often is associated with
significant cognitive dysfunction. We conducted a
meta-analysis of genome-wide interaction of MDD and
cognitive function using data from four large European
cohorts in a total of 3510 MDD cases and 6057 controls. In
addition, we conducted analyses using polygenic risk scores
(PRS) based on data from the Psychiatric Genomics Consortium
(PGC) on the traits of MDD, Bipolar disorder (BD),
Schizophrenia (SCZ), and mood instability (MIN). Functional
exploration contained gene expression analyses and Ingenuity
Pathway Analysis (IPA®). We identified a set of
significantly interacting single nucleotide polymorphisms
(SNPs) between MDD and the genome-wide association study
(GWAS) of cognitive domains of executive function,
processing speed, and global cognition. Several of these
SNPs are located in genes expressed in brain, with important
roles such as neuronal development (REST), oligodendrocyte
maturation (TNFRSF21), and myelination (ARFGEF1). IPA®
identified a set of core genes from our dataset that mapped
to a wide range of canonical pathways and biological
functions (MPO, FOXO1, PDE3A, TSLP, NLRP9, ADAMTS5, ROBO1,
REST). Furthermore, IPA® identified upstream regulator
molecules and causal networks impacting on the expression of
dataset genes, providing a genetic basis for further
clinical exploration (vitamin D receptor, beta-estradiol,
tadalafil). PRS of MIN and meta-PRS of MDD, MIN and SCZ were
significantly associated with all cognitive domains. Our
results suggest several genes involved in physiological
processes for the development and maintenance of cognition
in MDD, as well as potential novel therapeutic agents that
could be explored in patients with MDD associated cognitive
dysfunction.},
cin = {INM-1},
ddc = {610},
cid = {I:(DE-Juel1)INM-1-20090406},
pnm = {5251 - Multilevel Brain Organization and Variability
(POF4-525)},
pid = {G:(DE-HGF)POF4-5251},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34782712},
UT = {WOS:000718698500001},
doi = {10.1038/s41380-021-01379-5},
url = {https://juser.fz-juelich.de/record/903474},
}