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000903474 1001_ $$0P:(DE-HGF)0$$aThalamuthu, Anbupalam$$b0
000903474 245__ $$aGenome-wide interaction study with major depression identifies novel variants associated with cognitive function
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000903474 520__ $$aMajor Depressive Disorder (MDD) often is associated with significant cognitive dysfunction. We conducted a meta-analysis of genome-wide interaction of MDD and cognitive function using data from four large European cohorts in a total of 3510 MDD cases and 6057 controls. In addition, we conducted analyses using polygenic risk scores (PRS) based on data from the Psychiatric Genomics Consortium (PGC) on the traits of MDD, Bipolar disorder (BD), Schizophrenia (SCZ), and mood instability (MIN). Functional exploration contained gene expression analyses and Ingenuity Pathway Analysis (IPA®). We identified a set of significantly interacting single nucleotide polymorphisms (SNPs) between MDD and the genome-wide association study (GWAS) of cognitive domains of executive function, processing speed, and global cognition. Several of these SNPs are located in genes expressed in brain, with important roles such as neuronal development (REST), oligodendrocyte maturation (TNFRSF21), and myelination (ARFGEF1). IPA® identified a set of core genes from our dataset that mapped to a wide range of canonical pathways and biological functions (MPO, FOXO1, PDE3A, TSLP, NLRP9, ADAMTS5, ROBO1, REST). Furthermore, IPA® identified upstream regulator molecules and causal networks impacting on the expression of dataset genes, providing a genetic basis for further clinical exploration (vitamin D receptor, beta-estradiol, tadalafil). PRS of MIN and meta-PRS of MDD, MIN and SCZ were significantly associated with all cognitive domains. Our results suggest several genes involved in physiological processes for the development and maintenance of cognition in MDD, as well as potential novel therapeutic agents that could be explored in patients with MDD associated cognitive dysfunction.
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000903474 7001_ $$00000-0003-3255-5118$$aMills, Natalie T.$$b1
000903474 7001_ $$0P:(DE-HGF)0$$aBerger, Klaus$$b2
000903474 7001_ $$0P:(DE-HGF)0$$aMinnerup, Heike$$b3
000903474 7001_ $$0P:(DE-HGF)0$$aGrotegerd, Dominik$$b4
000903474 7001_ $$0P:(DE-HGF)0$$aDannlowski, Udo$$b5
000903474 7001_ $$0P:(DE-HGF)0$$aMeinert, Susanne$$b6
000903474 7001_ $$0P:(DE-HGF)0$$aOpel, Nils$$b7
000903474 7001_ $$0P:(DE-HGF)0$$aRepple, Jonathan$$b8
000903474 7001_ $$0P:(DE-HGF)0$$aGruber, Marius$$b9
000903474 7001_ $$aNenadić, Igor$$b10
000903474 7001_ $$aStein, Frederike$$b11
000903474 7001_ $$aBrosch, Katharina$$b12
000903474 7001_ $$aMeller, Tina$$b13
000903474 7001_ $$aPfarr, Julia-Katharina$$b14
000903474 7001_ $$0P:(DE-Juel1)186755$$aForstner, Andreas J.$$b15
000903474 7001_ $$aHoffmann, Per$$b16
000903474 7001_ $$00000-0002-8770-2464$$aNöthen, Markus M.$$b17
000903474 7001_ $$00000-0002-1571-1468$$aWitt, Stephanie$$b18
000903474 7001_ $$00000-0002-5236-6149$$aRietschel, Marcella$$b19
000903474 7001_ $$aKircher, Tilo$$b20
000903474 7001_ $$00000-0002-3599-6018$$aAdams, Mark$$b21
000903474 7001_ $$00000-0002-0198-4588$$aMcIntosh, Andrew M.$$b22
000903474 7001_ $$00000-0003-1249-6106$$aPorteous, David J.$$b23
000903474 7001_ $$00000-0002-1733-263X$$aDeary, Ian J.$$b24
000903474 7001_ $$00000-0002-9405-9550$$aHayward, Caroline$$b25
000903474 7001_ $$00000-0003-0198-5078$$aCampbell, Archie$$b26
000903474 7001_ $$00000-0003-3684-4208$$aGrabe, Hans Jörgen$$b27
000903474 7001_ $$00000-0002-8309-094X$$aTeumer, Alexander$$b28
000903474 7001_ $$aHomuth, Georg$$b29
000903474 7001_ $$00000-0002-1757-7768$$avan der Auwera-Palitschka, Sandra$$b30
000903474 7001_ $$00000-0003-1690-0209$$aOliver Schubert, K.$$b31
000903474 7001_ $$0P:(DE-HGF)0$$aBaune, Bernhard T.$$b32$$eCorresponding author
000903474 773__ $$0PERI:(DE-600)1502531-7$$a10.1038/s41380-021-01379-5$$p1111–1119$$tMolecular psychiatry$$v27$$x1359-4184$$y2022
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000903474 8564_ $$uhttps://juser.fz-juelich.de/record/903474/files/Thalamuthu_GWAS_Cogn_MDD-clean-Final_NM_BB.pdf$$yPublished on 2021-11-15. Available in OpenAccess from 2022-05-15.
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