Mendelian Randomization Reveals Interleukin-6 Receptor-Lipoprotein(a) Interplay With Independent Cardiovascular Risk Reductions

In the study at hand, 2-sample Mendelian randomization supported a causal effect of interleukin-6 receptor (IL-6R) signaling on Lp(a) concentrations, revealing a direct interplay between 2 causal risk factors for cardiovascular disease (CVD). Importantly, epidemiological analyses in UK Biobank showed that neglecting the IL-6R functional state can confound the association between IL-6 levels and Lp(a). However, the effect of circulating IL-6 on Lp(a) concentrations was modest even when the functional state of the receptor was considered. In line, factorial Mendelian randomization indicated that down-regulation of IL-6R signaling and Lp(a) independently reduce CVD risk, highlighting complementary opportunities for CVD risk mitigation.