Investigating evidence for a causal association between inflammation and self-harm: A multivariable Mendelian Randomisation study
Open accessAbstract
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: ). 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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Only very few studies have investigated the relationship between NSSI and inflammation.
“Until very recently, only very few studies investigated the relationship between NSSI and inflammation.”
From Elevated levels of monocyte-lymphocyte ratio and platelet-lymphocyte ratio in adolescents with non-suicidal self-injury (2022) · cites this paper as [12]
Results on the relationship between inflammation and NSSI are conflicting among different studies.
“However, results are conflicting among different studies.”
From Elevated levels of monocyte-lymphocyte ratio and platelet-lymphocyte ratio in adolescents with non-suicidal self-injury (2022) · cites this paper as [12]
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Ellinghaus, D. (2022) · Cambridge Prisms Precision Medicine · doi:10.1017/pcm.2022.12.pr1
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Алфимова, М. В., Лежейко, Т. В., Gabaeva, M. V., Plakunova, V., Mikhailova, V. A., Каледа, В. Г., & Голимбет, В. Е. (2023) · Генетика · doi:10.31857/s0016675823020029
SNP-Associated Differential Methylation in ARHGEF38: Insights into Genetic-Epigenetic InteractionsPreprint
Kovács, E. H. C., Casten, L. G., Mullins, N., Richards, J. G., Williams, A. J., Wemmie, J. A., Magnotta, V. A., Fiedorowicz, J., Michaelson, J. J., & Gaine, M. E. (2025) · medRxiv · doi:10.1101/2025.02.28.25322876
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SNP-associated differential methylation in ARHGEF38 : insights into genetic-epigenetic interactions
Kovács, E. H. C., Casten, L. G., Mullins, N., Richards, J. G., Williams, A. J., Wemmie, J. A., Magnotta, V. A., Fiedorowicz, J. G., Michaelson, J. J., & Gaine, M. E. (2025) · Epigenomics · doi:10.1080/17501911.2025.2513215
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- Authors
- Russell, A. E., Ford, T., Gunnell, D., Heron, J., Joinson, C., Moran, P., Relton, C., Suderman, M., Hemani, G., & Mars, B.
- Affiliations
- University of Bristol (GB)
- University of Cambridge (GB)
- University Hospitals Bristol NHS Foundation Trust (GB)
- Corresponding author
- Russell, Abigail Emma
- ORCID
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2020-10
- Volume
- 89
- Pages
- 43-50
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC7575900
- OpenAlex
- W3028962909
- Cited by
- 39
- References
- 58
- Citations by year
- 2025: 10 · 2024: 7 · 2023: 6 · 2022: 15 · 2021: 1
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Brain Behavior and Immunity (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Open Research Exeter (University of Exeter) (publishedVersion, cc-by)
- Bristol Research (University of Bristol) (acceptedVersion, cc-by)
- Figshare (submittedVersion, cc-by)
- Explore Bristol Research (submittedVersion, cc-by)
- Apollo (University of Cambridge) (submittedVersion, cc-by-nc-nd)
- Apollo
- Funders
- Wellcome Trust (102215/2/13/2, 208806/Z/17/Z, GR067797MA)
- University of Bristol
- Medical Research Council (MR/R004889/1, IL-6)
- National Institute for Health Research
- University Hospitals Bristol NHS Foundation Trust
- Topics
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- self-harm, inflammation, interleukin-6, C-reactive protein, suicidal intent, suicide risk, causal relationship, genetic susceptibility, inflammatory markers
- MeSH terms
- Humans, Inflammation, Self-Injurious Behavior, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Mendelian Randomization Analysis
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