Manuel Mattheisen

Using genetic drug-target networks to develop new drug hypotheses for major depressive disorder

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

Using genetic drug-target networks to develop new drug hypotheses for major depressive disorder. / Gaspar, Héléna A; Gerring, Zachary; Hübel, Christopher; Middeldorp, Christel M; Derks, Eske M; Breen, Gerome; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.

In: Translational Psychiatry, Vol. 9, No. 1, 117, 2019.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Gaspar, HA, Gerring, Z, Hübel, C, Middeldorp, CM, Derks, EM, Breen, G & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium 2019, 'Using genetic drug-target networks to develop new drug hypotheses for major depressive disorder', Translational Psychiatry, vol. 9, no. 1, 117. https://doi.org/10.1038/s41398-019-0451-4

APA

Gaspar, H. A., Gerring, Z., Hübel, C., Middeldorp, C. M., Derks, E. M., Breen, G., & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (2019). Using genetic drug-target networks to develop new drug hypotheses for major depressive disorder. Translational Psychiatry, 9(1), [117]. https://doi.org/10.1038/s41398-019-0451-4

CBE

Gaspar HA, Gerring Z, Hübel C, Middeldorp CM, Derks EM, Breen G, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. 2019. Using genetic drug-target networks to develop new drug hypotheses for major depressive disorder. Translational Psychiatry. 9(1):Article 117. https://doi.org/10.1038/s41398-019-0451-4

MLA

Vancouver

Gaspar HA, Gerring Z, Hübel C, Middeldorp CM, Derks EM, Breen G et al. Using genetic drug-target networks to develop new drug hypotheses for major depressive disorder. Translational Psychiatry. 2019;9(1). 117. https://doi.org/10.1038/s41398-019-0451-4

Author

Gaspar, Héléna A ; Gerring, Zachary ; Hübel, Christopher ; Middeldorp, Christel M ; Derks, Eske M ; Breen, Gerome ; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. / Using genetic drug-target networks to develop new drug hypotheses for major depressive disorder. In: Translational Psychiatry. 2019 ; Vol. 9, No. 1.

Bibtex

@article{094338759eb8443cb4166b5474b79a39,
title = "Using genetic drug-target networks to develop new drug hypotheses for major depressive disorder",
abstract = "The major depressive disorder (MDD) working group of the Psychiatric Genomics Consortium (PGC) has published a genome-wide association study (GWAS) for MDD in 130,664 cases, identifying 44 risk variants. We used these results to investigate potential drug targets and repurposing opportunities. We built easily interpretable bipartite drug-target networks integrating interactions between drugs and their targets, genome-wide association statistics, and genetically predicted expression levels in different tissues, using the online tool Drug Targetor ( drugtargetor.com ). We also investigated drug-target relationships that could be impacting MDD. MAGMA was used to perform pathway analyses and S-PrediXcan to investigate the directionality of tissue-specific expression levels in patients vs. controls. Outside the major histocompatibility complex (MHC) region, 153 protein-coding genes are significantly associated with MDD in MAGMA after multiple testing correction; among these, five are predicted to be down or upregulated in brain regions and 24 are known druggable genes. Several drug classes were significantly enriched, including monoamine reuptake inhibitors, sex hormones, antipsychotics, and antihistamines, indicating an effect on MDD and potential repurposing opportunities. These findings not only require validation in model systems and clinical examination, but also show that GWAS may become a rich source of new therapeutic hypotheses for MDD and other psychiatric disorders that need new-and better-treatment options.",
keywords = "ASSOCIATION, EFFICACY, GENDER-DIFFERENCES, KETAMINE, PLACEBO, PREGABALIN, RALOXIFENE, RECEPTOR MODULATORS, SIGNATURES, TRIAL",
author = "Gaspar, {H{\'e}l{\'e}na A} and Zachary Gerring and Christopher H{\"u}bel and Middeldorp, {Christel M} and Derks, {Eske M} and Gerome Breen and {Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium} and Manuel Mattheisen and Esben Agerbo and Buttensch{\o}n, {Henriette N{\o}rm{\o}lle} and Christensen, {Jane Hvarregaard} and Jakob Grove and Pedersen, {Carsten B{\o}cker} and Pedersen, {Marianne Gi{\o}rtz} and Per Qvist and Ole Mors and Mortensen, {Preben Bo} and Anders B{\o}rglum",
year = "2019",
doi = "10.1038/s41398-019-0451-4",
language = "English",
volume = "9",
journal = "Translational Psychiatry",
issn = "2158-3188",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Using genetic drug-target networks to develop new drug hypotheses for major depressive disorder

AU - Gaspar, Héléna A

AU - Gerring, Zachary

AU - Hübel, Christopher

AU - Middeldorp, Christel M

AU - Derks, Eske M

AU - Breen, Gerome

AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

AU - Mattheisen, Manuel

AU - Agerbo, Esben

AU - Buttenschøn, Henriette Nørmølle

AU - Christensen, Jane Hvarregaard

AU - Grove, Jakob

AU - Pedersen, Carsten Bøcker

AU - Pedersen, Marianne Giørtz

AU - Qvist, Per

AU - Mors, Ole

AU - Mortensen, Preben Bo

AU - Børglum, Anders

PY - 2019

Y1 - 2019

N2 - The major depressive disorder (MDD) working group of the Psychiatric Genomics Consortium (PGC) has published a genome-wide association study (GWAS) for MDD in 130,664 cases, identifying 44 risk variants. We used these results to investigate potential drug targets and repurposing opportunities. We built easily interpretable bipartite drug-target networks integrating interactions between drugs and their targets, genome-wide association statistics, and genetically predicted expression levels in different tissues, using the online tool Drug Targetor ( drugtargetor.com ). We also investigated drug-target relationships that could be impacting MDD. MAGMA was used to perform pathway analyses and S-PrediXcan to investigate the directionality of tissue-specific expression levels in patients vs. controls. Outside the major histocompatibility complex (MHC) region, 153 protein-coding genes are significantly associated with MDD in MAGMA after multiple testing correction; among these, five are predicted to be down or upregulated in brain regions and 24 are known druggable genes. Several drug classes were significantly enriched, including monoamine reuptake inhibitors, sex hormones, antipsychotics, and antihistamines, indicating an effect on MDD and potential repurposing opportunities. These findings not only require validation in model systems and clinical examination, but also show that GWAS may become a rich source of new therapeutic hypotheses for MDD and other psychiatric disorders that need new-and better-treatment options.

AB - The major depressive disorder (MDD) working group of the Psychiatric Genomics Consortium (PGC) has published a genome-wide association study (GWAS) for MDD in 130,664 cases, identifying 44 risk variants. We used these results to investigate potential drug targets and repurposing opportunities. We built easily interpretable bipartite drug-target networks integrating interactions between drugs and their targets, genome-wide association statistics, and genetically predicted expression levels in different tissues, using the online tool Drug Targetor ( drugtargetor.com ). We also investigated drug-target relationships that could be impacting MDD. MAGMA was used to perform pathway analyses and S-PrediXcan to investigate the directionality of tissue-specific expression levels in patients vs. controls. Outside the major histocompatibility complex (MHC) region, 153 protein-coding genes are significantly associated with MDD in MAGMA after multiple testing correction; among these, five are predicted to be down or upregulated in brain regions and 24 are known druggable genes. Several drug classes were significantly enriched, including monoamine reuptake inhibitors, sex hormones, antipsychotics, and antihistamines, indicating an effect on MDD and potential repurposing opportunities. These findings not only require validation in model systems and clinical examination, but also show that GWAS may become a rich source of new therapeutic hypotheses for MDD and other psychiatric disorders that need new-and better-treatment options.

KW - ASSOCIATION

KW - EFFICACY

KW - GENDER-DIFFERENCES

KW - KETAMINE

KW - PLACEBO

KW - PREGABALIN

KW - RALOXIFENE

KW - RECEPTOR MODULATORS

KW - SIGNATURES

KW - TRIAL

U2 - 10.1038/s41398-019-0451-4

DO - 10.1038/s41398-019-0451-4

M3 - Journal article

C2 - 30877270

VL - 9

JO - Translational Psychiatry

JF - Translational Psychiatry

SN - 2158-3188

IS - 1

M1 - 117

ER -