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@article{Inkster:2018:10.1097/YPG.0000000000000203,
author = {Inkster, B and Simmons, A and Cole, JH and Schoof, E and Linding, R and Nichols, T and Muglia, P and Holsboer, F and Saemann, PG and McGuffin, P and Fu, CHY and Miskowiak, K and Matthews, PM and Zai, G and Nicodemus, K},
doi = {10.1097/YPG.0000000000000203},
journal = {Psychiatric Genetics},
pages = {77--84},
title = {Unravelling the GSK3 beta-related genotypic interaction network influencing hippocampal volume in recurrent major depressive disorder},
url = {http://dx.doi.org/10.1097/YPG.0000000000000203},
volume = {28},
year = {2018}
}

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TY  - JOUR
AB  - Objective Glycogen synthase kinase 3β (GSK3β) has been implicated in mood disorders. We previously reported associations between a GSK3β polymorphism and hippocampal volume in major depressive disorder (MDD). We then reported similar associations for a subset of GSK3β-regulated genes. We now investigate an algorithm-derived comprehensive list of genes encoding proteins that directly interact with GSK3β to identify a genotypic network influencing hippocampal volume in MDD.Participants and methods We used discovery (N=141) and replication (N=77) recurrent MDD samples. Our gene list was generated from the NetworKIN database. Hippocampal measures were derived using an optimized Freesurfer protocol. We identified interacting single nucleotide polymorphisms using the machine learning algorithm Random Forest and verified interactions using likelihood ratio tests between nested linear regression models.Results The discovery sample showed multiple two-single nucleotide polymorphism interactions with hippocampal volume. The replication sample showed a replicable interaction (likelihood ratio test: P=0.0088, replication sample; P=0.017, discovery sample; Stouffer’s combined P=0.0007) between genes associated previously with endoplasmic reticulum stress, calcium regulation and histone modifications.Conclusion Our results provide genetic evidence supporting associations between hippocampal volume and MDD, which may reflect underlying cellular stress responses. Our study provides evidence of biological mechanisms that should be further explored in the search for disease-modifying therapeutic targets for depression.
AU  - Inkster,B
AU  - Simmons,A
AU  - Cole,JH
AU  - Schoof,E
AU  - Linding,R
AU  - Nichols,T
AU  - Muglia,P
AU  - Holsboer,F
AU  - Saemann,PG
AU  - McGuffin,P
AU  - Fu,CHY
AU  - Miskowiak,K
AU  - Matthews,PM
AU  - Zai,G
AU  - Nicodemus,K
DO  - 10.1097/YPG.0000000000000203
EP  - 84
PY  - 2018///
SN  - 0955-8829
SP  - 77
TI  - Unravelling the GSK3 beta-related genotypic interaction network influencing hippocampal volume in recurrent major depressive disorder
T2  - Psychiatric Genetics
UR  - http://dx.doi.org/10.1097/YPG.0000000000000203
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000445631900001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/72479
VL  - 28
ER  -

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