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Investigating evidence for a causal association between inflammation and self-harm: A multivariable Mendelian Randomisation study

BACKGROUND: The causal role of inflammatory markers on self-harm and suicidal risk has been studied using observational data, with conflicting results. Confounding and reverse causation can lead to bias, so we appraised question from a genetic perspective to protect against these biases. We measured...

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Autores principales: Russell, Abigail Emma, Ford, Tamsin, Gunnell, David, Heron, Jon, Joinson, Carol, Moran, Paul, Relton, Caroline, Suderman, Matthew, Hemani, Gibran, Mars, Becky
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575900/
https://www.ncbi.nlm.nih.gov/pubmed/32473944
http://dx.doi.org/10.1016/j.bbi.2020.05.065
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author Russell, Abigail Emma
Ford, Tamsin
Gunnell, David
Heron, Jon
Joinson, Carol
Moran, Paul
Relton, Caroline
Suderman, Matthew
Hemani, Gibran
Mars, Becky
author_facet Russell, Abigail Emma
Ford, Tamsin
Gunnell, David
Heron, Jon
Joinson, Carol
Moran, Paul
Relton, Caroline
Suderman, Matthew
Hemani, Gibran
Mars, Becky
author_sort Russell, Abigail Emma
collection PubMed
description BACKGROUND: The causal role of inflammatory markers on self-harm and suicidal risk has been studied using observational data, with conflicting results. Confounding and reverse causation can lead to bias, so we appraised question from a genetic perspective to protect against these biases. We measured associations between genetic liability for high levels of inflammatory markers Interleukin-6 (IL-6) and C-reactive protein (CRP) on self-harm, and conducted a secondary analysis restricted to self-harm with suicidal intent. METHODS: We conducted two sample and multivariable Mendelian randomisation (MR) to assess the effects of IL-6 and CRP on self-harm utilising existing data and conducting new genome wide association studies to instrument IL-6 and CRP, and for the outcome of self-harm. RESULTS: No single nucleotide polymorphisms (SNPs) reached genome-wide significance for self-harm, however 193 SNPs met suggestive significance levels (p < 5 × 10(−6)). We found no evidence of an association between our instruments for IL-6 and self-harm in the two-sample MR, however we found an inverse association between instruments for CRP and self-harm, indicating that higher levels of circulating CRP may protect against self-harm (inverse variance weighted OR 0.92, 95%CI 0.84, 1.01, p = 0.08; MR Egger OR 0.86, 95% CI 0.74, 1.00, p = 0.05). The direct effect estimate for IL-6 was slightly smaller in the multivariable MR than in the two sample MR, while the CRP effect estimates were consistent with the two sample MR (OR 0.92, SE 1.05, p = 0.09). CONCLUSIONS: Our findings are conflicting and indicate that IL-6 and CRP are not robust etiological markers of increased self-harm or suicide risk.
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spelling pubmed-75759002020-10-23 Investigating evidence for a causal association between inflammation and self-harm: A multivariable Mendelian Randomisation study Russell, Abigail Emma Ford, Tamsin Gunnell, David Heron, Jon Joinson, Carol Moran, Paul Relton, Caroline Suderman, Matthew Hemani, Gibran Mars, Becky Brain Behav Immun Article BACKGROUND: The causal role of inflammatory markers on self-harm and suicidal risk has been studied using observational data, with conflicting results. Confounding and reverse causation can lead to bias, so we appraised question from a genetic perspective to protect against these biases. We measured associations between genetic liability for high levels of inflammatory markers Interleukin-6 (IL-6) and C-reactive protein (CRP) on self-harm, and conducted a secondary analysis restricted to self-harm with suicidal intent. METHODS: We conducted two sample and multivariable Mendelian randomisation (MR) to assess the effects of IL-6 and CRP on self-harm utilising existing data and conducting new genome wide association studies to instrument IL-6 and CRP, and for the outcome of self-harm. RESULTS: No single nucleotide polymorphisms (SNPs) reached genome-wide significance for self-harm, however 193 SNPs met suggestive significance levels (p < 5 × 10(−6)). We found no evidence of an association between our instruments for IL-6 and self-harm in the two-sample MR, however we found an inverse association between instruments for CRP and self-harm, indicating that higher levels of circulating CRP may protect against self-harm (inverse variance weighted OR 0.92, 95%CI 0.84, 1.01, p = 0.08; MR Egger OR 0.86, 95% CI 0.74, 1.00, p = 0.05). The direct effect estimate for IL-6 was slightly smaller in the multivariable MR than in the two sample MR, while the CRP effect estimates were consistent with the two sample MR (OR 0.92, SE 1.05, p = 0.09). CONCLUSIONS: Our findings are conflicting and indicate that IL-6 and CRP are not robust etiological markers of increased self-harm or suicide risk. Elsevier 2020-10 /pmc/articles/PMC7575900/ /pubmed/32473944 http://dx.doi.org/10.1016/j.bbi.2020.05.065 Text en © 2020 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Russell, Abigail Emma
Ford, Tamsin
Gunnell, David
Heron, Jon
Joinson, Carol
Moran, Paul
Relton, Caroline
Suderman, Matthew
Hemani, Gibran
Mars, Becky
Investigating evidence for a causal association between inflammation and self-harm: A multivariable Mendelian Randomisation study
title Investigating evidence for a causal association between inflammation and self-harm: A multivariable Mendelian Randomisation study
title_full Investigating evidence for a causal association between inflammation and self-harm: A multivariable Mendelian Randomisation study
title_fullStr Investigating evidence for a causal association between inflammation and self-harm: A multivariable Mendelian Randomisation study
title_full_unstemmed Investigating evidence for a causal association between inflammation and self-harm: A multivariable Mendelian Randomisation study
title_short Investigating evidence for a causal association between inflammation and self-harm: A multivariable Mendelian Randomisation study
title_sort investigating evidence for a causal association between inflammation and self-harm: a multivariable mendelian randomisation study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575900/
https://www.ncbi.nlm.nih.gov/pubmed/32473944
http://dx.doi.org/10.1016/j.bbi.2020.05.065
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