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Tytuł:
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Depression and interleukin-6 signaling: A Mendelian Randomization study.
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Autorzy:
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Kelly KM; Department of Epidemiology, School of Public Health, University of Michigan, United States; Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, The Netherlands. Electronic address: .
Smith JA; Department of Epidemiology, School of Public Health, University of Michigan, United States; Institute for Social Research, University of Michigan, United States.
Mezuk B; Department of Epidemiology, School of Public Health, University of Michigan, United States; Institute for Social Research, University of Michigan, United States.
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Źródło:
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Brain, behavior, and immunity [Brain Behav Immun] 2021 Jul; Vol. 95, pp. 106-114. Date of Electronic Publication: 2021 Feb 23.
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Typ publikacji:
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Journal Article; Research Support, N.I.H., Extramural
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Język:
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English
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Imprint Name(s):
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Publication: <2000- > : Amsterdam : Elsevier
Original Publication: San Diego : Academic Press, [c1987-
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MeSH Terms:
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Interleukin-6*/genetics
Receptors, Interleukin-6*/genetics
Animals ; Cytokine Receptor gp130 ; Depression/genetics ; Mendelian Randomization Analysis
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Grant Information:
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K01 MH093642 United States MH NIMH NIH HHS
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Contributed Indexing:
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Keywords: Depression; Inflammation; Interleukin-6; Mendelian Randomization; Soluble interleukin-6 receptor; sIL-6R
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Substance Nomenclature:
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0 (Interleukin-6)
0 (Receptors, Interleukin-6)
133483-10-0 (Cytokine Receptor gp130)
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Entry Date(s):
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Date Created: 20210225 Date Completed: 20210623 Latest Revision: 20210623
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Update Code:
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20240105
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DOI:
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10.1016/j.bbi.2021.02.019
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PMID:
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33631287
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Background: A large body of research has reported associations between depression and elevated interleukin-6 (IL-6), a cytokine with several roles including pro-inflammatory signaling. The nature and directionality of this relationship are not yet clear. In this study we use Mendelian Randomization to examine the possibility of a causal relationship between IL-6 and depressive symptoms, and to explore multiple signaling pathways that could serve as mechanisms for this relationship.
Methods: This study uses a two-sample Mendelian Randomization design. Data come from the UK Biobank (n = 89,119) and published summary statistics from six existing GWAS analyses. The primary analysis focuses on the soluble interleukin-6 receptor (sIL-6R), which is involved in multiple signaling pathways. Exploratory analyses use C-reactive protein (CRP) and soluble glycoprotein 130 (sgp130) to further examine potential underlying mechanisms.
Results: Results are consistent with a causal effect of sIL-6R on depression (PCA-IVW Odds Ratio: 1.023 (95% Confidence Interval: 1.006-1.039), p = 0.006). Exploratory analyses demonstrate that the relationship could be consistent with either decreased classical signaling or increased trans signaling as the underlying mechanism.
Discussion: These results strengthen the body evidence implicating IL-6 signaling in depression. When compared with existing observational and animal findings, the direction of these results suggests involvement of IL-6 trans signaling. Further study is needed to examine whether IL6R genetic variants might influence IL-6 trans signaling in the brain, as well as to explore other potential pathways linking depression and inflammation.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
