Investigating evidence for a causal association between inflammation and self-harm: A multivariable Mendelian...

Area of Science:

• Genetics
• Psychiatry
• Immunology

Background:

• Observational studies on inflammatory markers and self-harm risk yield conflicting results.
• Confounding and reverse causation are limitations of observational studies.
• Genetic approaches, like Mendelian randomization, can mitigate bias in etiological research.

Purpose of the Study:

• To investigate the causal role of inflammatory markers, Interleukin-6 (IL-6) and C-reactive protein (CRP), in self-harm using a genetic perspective.
• To address biases inherent in observational studies of self-harm etiology.
• To conduct a secondary analysis on self-harm with suicidal intent.

Main Methods:

• Two-sample and multivariable Mendelian randomization (MR) were employed.
• Genome-wide association studies (GWAS) were used to identify genetic instruments for IL-6 and CRP.
• Associations between genetic liability for IL-6/CRP and self-harm outcomes were assessed.

Main Results:

• No single nucleotide polymorphisms (SNPs) reached genome-wide significance for self-harm.
• No evidence of association was found between IL-6 genetic liability and self-harm.
• An inverse association between CRP genetic liability and self-harm was observed, suggesting a potential protective effect (OR 0.92, 95% CI 0.84-1.01).

Conclusions:

• Findings suggest that IL-6 and CRP are not robust etiological markers for increased self-harm risk.
• The causal link between these inflammatory markers and self-harm requires further investigation.
• Genetic evidence does not support a significant causal role for IL-6 or CRP in self-harm.