Investigating evidence for a causal association between inflammation and self-harm: A multivariable Mendelian Randomisation study
dc.contributor.author | Russell, AE | |
dc.contributor.author | Ford, T | |
dc.contributor.author | Gunnell, D | |
dc.contributor.author | Heron, J | |
dc.contributor.author | Joinson, C | |
dc.contributor.author | Moran, P | |
dc.contributor.author | Relton, C | |
dc.contributor.author | Suderman, M | |
dc.contributor.author | Hemani, G | |
dc.contributor.author | Mars, B | |
dc.date.accessioned | 2020-07-06T14:09:54Z | |
dc.date.issued | 2020-05-28 | |
dc.description.abstract | 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. | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.description.sponsorship | Wellcome Trust | en_GB |
dc.description.sponsorship | National Institute for Health Research (NIHR) | en_GB |
dc.identifier.citation | Published online 28 May 2020 | en_GB |
dc.identifier.doi | 10.1016/j.bbi.2020.05.065 | |
dc.identifier.grantnumber | MR/R004889/1 | en_GB |
dc.identifier.grantnumber | 102215/2/13/2 | en_GB |
dc.identifier.grantnumber | GR067797MA | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/121798 | |
dc.language.iso | en | en_GB |
dc.publisher | Elsevier | en_GB |
dc.rights | © 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/). | en_GB |
dc.subject | C-reactive protein | en_GB |
dc.subject | self harm | en_GB |
dc.subject | suicide | en_GB |
dc.subject | Mendelian Randomisation | en_GB |
dc.subject | Inflammation | en_GB |
dc.subject | Interleukin-6 | en_GB |
dc.title | Investigating evidence for a causal association between inflammation and self-harm: A multivariable Mendelian Randomisation study | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2020-07-06T14:09:54Z | |
dc.identifier.issn | 0889-1591 | |
dc.description | This is the final version. Available on open access from Elsevier via the DOI in this record | en_GB |
dc.identifier.journal | Brain, Behavior, and Immunity | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2020-05-24 | |
exeter.funder | ::Medical Research Council (MRC) | en_GB |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2020-05-24 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2020-07-06T13:59:08Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2020-07-15T14:31:25Z | |
refterms.panel | A | en_GB |
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Except where otherwise noted, this item's licence is described as © 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/).