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Unravelling the GSK3β-related genotypic interaction network influencing hippocampal volume in recurrent major depressive disorder

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Inkster, B, Simmons, A, Cole, JH, Schoof, E, Linding, R, Nichols, T, Muglia, P, Holsboer, F, Sämann, PG, McGuffin, P, Fu, CHY, Miskowiak, K, Matthews, PM, Zai, G & Nicodemus, K 2018, 'Unravelling the GSK3β-related genotypic interaction network influencing hippocampal volume in recurrent major depressive disorder' Psychiatric Genetics, bind 28, nr. 5, s. 77-84. https://doi.org/10.1097/YPG.0000000000000203

APA

CBE

Inkster B, Simmons A, Cole JH, Schoof E, Linding R, Nichols T, Muglia P, Holsboer F, Sämann PG, McGuffin P, Fu CHY, Miskowiak K, Matthews PM, Zai G, Nicodemus K. 2018. Unravelling the GSK3β-related genotypic interaction network influencing hippocampal volume in recurrent major depressive disorder. Psychiatric Genetics. 28(5):77-84. https://doi.org/10.1097/YPG.0000000000000203

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Author

Inkster, Becky ; Simmons, Andy ; Cole, James H ; Schoof, Erwin ; Linding, Rune ; Nichols, Tom ; Muglia, Pierandrea ; Holsboer, Florian ; Sämann, Philipp G ; McGuffin, Peter ; Fu, Cynthia H Y ; Miskowiak, Kamilla ; Matthews, Paul M ; Zai, Gwyneth ; Nicodemus, Kristin. / Unravelling the GSK3β-related genotypic interaction network influencing hippocampal volume in recurrent major depressive disorder. I: Psychiatric Genetics. 2018 ; Bind 28, Nr. 5. s. 77-84.

Bibtex

@article{63c9079280f14c5f8f5c8476de8badcb,
title = "Unravelling the GSK3β-related genotypic interaction network influencing hippocampal volume in recurrent major depressive disorder",
abstract = "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.",
author = "Becky Inkster and Andy Simmons and Cole, {James H} and Erwin Schoof and Rune Linding and Tom Nichols and Pierandrea Muglia and Florian Holsboer and S{\"a}mann, {Philipp G} and Peter McGuffin and Fu, {Cynthia H Y} and Kamilla Miskowiak and Matthews, {Paul M} and Gwyneth Zai and Kristin Nicodemus",
year = "2018",
month = "10",
doi = "10.1097/YPG.0000000000000203",
language = "English",
volume = "28",
pages = "77--84",
journal = "Psychiatric Genetics",
issn = "0955-8829",
publisher = "Lippincott Williams & Wilkins",
number = "5",

}

RIS

TY - JOUR

T1 - Unravelling the GSK3β-related genotypic interaction network influencing hippocampal volume in recurrent major depressive disorder

AU - Inkster, Becky

AU - Simmons, Andy

AU - Cole, James H

AU - Schoof, Erwin

AU - Linding, Rune

AU - Nichols, Tom

AU - Muglia, Pierandrea

AU - Holsboer, Florian

AU - Sämann, Philipp G

AU - McGuffin, Peter

AU - Fu, Cynthia H Y

AU - Miskowiak, Kamilla

AU - Matthews, Paul M

AU - Zai, Gwyneth

AU - Nicodemus, Kristin

PY - 2018/10

Y1 - 2018/10

N2 - 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.

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.

U2 - 10.1097/YPG.0000000000000203

DO - 10.1097/YPG.0000000000000203

M3 - Journal article

VL - 28

SP - 77

EP - 84

JO - Psychiatric Genetics

JF - Psychiatric Genetics

SN - 0955-8829

IS - 5

ER -

ID: 55462178