Interleukin-6 (IL6) is a key pro-inflammatory cytokine involved in the acute-phase response and is associated with a number of diseases, including Type 2 Diabetes.

We plan to do an IL6 genome-wide association study meta-analysis of 1410 ALSPAC individuals with 1210 individuals from the InCHIANTI study. We will require IL6 levels, age and gender adjusted results and combine using an inverse variance approach. We will perform genome-wide analyses and also cis-effect analyses for variants in or near (+/- 300kb) the genes coding for IL6 or IL6R - encoding for the IL6 receptor. IL6R SNPs have been previously associated with IL6 levels and can act as positive controls (Melzer et. al 2008).

Having meta-analysed this data, we then plan to replicate our initial findings using ~5000 additional children with IL6 measured from the ALSPAC study in order to determine loci that are robustly associated with varying levels of IL6. Potentially, this may involve ~10 top hits (or candidate hits) from the meta-analysis, although the exact number of SNPs we will follow up will depend on the false discovery rate/QQ plot statistics.

Note also that the InCHIANTI study has been approached by another GWAS consortium looking at IL6 levels (based around the Sardinia study) with a view to replicating their results. In the event that the GWAS meta-analysis of ALSPAC and InCHIANTI does not produce any stand out results, we would suggest that the best next step will be to join ALSPAC and InCHIANTI into an expanded IL6 GWAS consortium. Although making the relative contribution of ALSPAC and INCHIANTI smaller, it will increase power substantially and help identify variants that influence IL6 levels, something that could be useful for Mendelian Randomisation studies.