Centre for Academic Mental Health, Population Health Sciences, University of Bristol Medical School, United Kingdom.
University of Cambridge, Department of Psychiatry, United Kingdom.
Brain Behav Immun. 2020 Oct;89:43-50. doi: 10.1016/j.bbi.2020.05.065. Epub 2020 May 28.
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.
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.
No single nucleotide polymorphisms (SNPs) reached genome-wide significance for self-harm, however 193 SNPs met suggestive significance levels (p < 5 × 10). 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).
Our findings are conflicting and indicate that IL-6 and CRP are not robust etiological markers of increased self-harm or suicide risk.
使用观察性数据研究了炎症标志物对自残和自杀风险的因果作用，但结果存在冲突。混杂和反向因果关系可能会导致偏差，因此我们从遗传角度评估问题，以防止这些偏差。我们测量了高水平炎症标志物白细胞介素-6 (IL-6) 和 C 反应蛋白 (CRP) 的遗传易感性与自残之间的关联，并进行了二次分析，仅限于有自杀意图的自残。
我们进行了两样本和多变量孟德尔随机化 (MR)，利用现有数据评估 IL-6 和 CRP 对自残的影响，并进行新的全基因组关联研究，以确定 IL-6 和 CRP 的影响因子，并评估自残的结果。
没有单个核苷酸多态性 (SNP) 达到自残的全基因组显著水平，但有 193 个 SNP 达到了有意义的水平 (p < 5 × 10)。我们在两样本 MR 中没有发现 IL-6 与自残之间的关联，但我们发现 CRP 与自残之间存在负相关，这表明循环 CRP 水平较高可能会预防自残 (逆方差加权 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)。多变量 MR 中的 IL-6 直接效应估计值略小于两样本 MR，而 CRP 的效应估计值与两样本 MR 一致 (OR 0.92，SE 1.05，p = 0.09)。
我们的研究结果存在矛盾，表明 IL-6 和 CRP 不是增加自残或自杀风险的稳健病因标志物。
