@article{ref1,
title="Investigating evidence for a causal association between inflammation and self-harm: a multivariable Mendelian Randomisation study",
journal="Brain, behavior, and immunity",
year="2020",
author="Emma Russell, Abigail and Ford, Tamsin and Gunnell, David and Heron, Jon and Joinson, Carol and Moran, Paul and Relton, Caroline and Suderman, Matthew and Hemani, Gibran and Mars, Becky",
volume="ePub",
number="ePub",
pages="ePub-ePub",
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<5x10-6). 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.<p /> <p>Language: en</p>",
language="en",
issn="0889-1591",
doi="10.1016/j.bbi.2020.05.065",
url="http://dx.doi.org/10.1016/j.bbi.2020.05.065"
}