PT  - JOURNAL ARTICLE
AU  - Fernando Pires Hartwig
AU  - Maria Carolina Borges
AU  - Bernardo Lessa Horta
AU  - Jack Bowden
AU  - George Davey Smith
TI  - Association between genetically elevated levels of inflammatory biomarkers and risk of schizophrenia: a two-sample Mendelian randomisation study
AID  - 10.1101/123976
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 123976
4099  - http://biorxiv.org/content/early/2017/04/10/123976.short
4100  - http://biorxiv.org/content/early/2017/04/10/123976.full
AB  - Background Positive associations between inflammatory biomarkers and risk of psychiatric disorders, including schizophrenia, have been reported in observational studies. However, conventional observational studies are prone to bias such as reverse causation and residual confounding.Methods In this study, we used summary data to evaluate the association of genetically elevated C reactive protein (CRP), interleukin-1 receptor antagonist (IL-1Ra) and soluble interleukin-6 receptor (IL-6R) levels with schizophrenia in a two-sample Mendelian randomisation design.Results The pooled odds ratio estimate using 18 CRP genetic instruments was 0.90 (95% CI: 0.84; 0.97) per two-fold increment in CRP levels; consistent results were obtained using different Mendelian randomisation methods and a more conservative set of instruments. The odds ratio for soluble IL-6R was 1.06 (95% CI: 1.01; 1.12) per two-fold increment. Estimates for IL-1Ra were inconsistent among instruments and pooled estimates were imprecise and centred on the null.Conclusion Under Mendelian randomisation assumptions, our findings suggest a protective causal effect of CRP and a risk-increasing causal effect of soluble IL-6R (potentially mediated at least in part by CRP) on schizophrenia risk.