| Title: | Investigating evidence for a causal association between inflammation and self-harm: A multivariable Mendelian Randomisation study |
| Journal: | Brain Behavior and Immunity |
| Published: | 28 May 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32473944/ |
| DOI: | https://doi.org/10.1016/j.bbi.2020.05.065 |
| Citations: | 19 (11 in last 2 years) as of 8 Aug 2024 |
Publication 9116
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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.</p>
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.</p>
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).</p>
CONCLUSIONS: Our findings are conflicting and indicate that IL-6 and CRP are not robust etiological markers of increased self-harm or suicide risk.</p>
10 Authors
- Abigail Emma Russell
- Tamsin Ford
- David Gunnell
- Jon Heron
- Carol Joinson
- Paul Moran
- Caroline Relton
- Matthew Suderman
- Gibran Hemani
- Becky Mars
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