Multi-biobank summary data Mendelian randomisation does not support a causal effect of IL-6 signalling on risk of pulmonary arterial hypertension

Abstract

In the most comprehensive analysis to date, this study failed to detect an association of genetically predicted CRP-weighted IL-6 signalling or CRP-weighted IL-6R signalling with PAH risk using all available PAH GWAS data https://bit.ly/3T5h5uj

FIGURE 1

Study overview and main results showing associations of C-reactive protein (CRP) weighted genetically proxied interleukin (IL)-6 signalling with pulmonary arterial hypertension (PAH) risk for each genetic variant stratified by genome-wide association study (GWAS) data source. Odds ratios represent the multiplicative increase in the odds of PAH per mg·L⁻¹ increase of genetically proxied CRP. In summary data Mendelian randomisation (MR) analyses, the effect of the exposure (CRP) on the outcome (PAH risk) is estimated by scaling the variant–outcome association (estimated in FinnGen, UK Biobank, and a 2019 meta-analysis) by the variant–exposure association (only estimated in the UK Biobank). The “rs” followed by a set of numbers (e.g. rs12730935) in this figure represent the variant-specific MR estimates from each GWAS for the 12 IL6R variants included in our analysis. The estimates of the “pooled IVW estimate” in grey is inverse variance weighted (IVW) meta-analysis of each GWAS's variant-specific effects. The estimates of the “pooled IVW estimate” in black is an IVW meta-analysis of the GWAS-specific effects.