The causality between C-reactive protein and asthma: A Two-Sample Mendelian Randomization Analysis

Abstract Background: C-reactive protein (CRP) plays a critical role in asthma development and is usually elevated in asthmatic patients. However, the causal association between CRP and asthma remains unknown. Results: We utilized single nucleotide polymorphisms (SNPs) associated with both CRP and outcomes of asthma, allergic asthma and obesity related asthma as genetic variables via genome-wide summary association study (GWAS). In our study, 42 SNPs were identified as instrumental variables (Ivs) for mendelian randomization (MR) analyses. According to the primary inference results by inverse variance weighted (IVW)methods, the circulating CRP was demonstrated to be significantly associated with risk of asthma (OR=1.046, 95%CI 1.004-1.090, P=0.030) and obesity related asthma (OR=1.072, 95%CI 1.009-1.138, P=0.025), whereas no distinct causality with allergic asthma (OR=1.051, 95%CI 0.994-1.112, P=0.081). Sensitivity analyses indicated that there’s no horizontal pleiotropy among IVs, and the MR results were proved to be robust by leave-one-out sensitivity analysis, despite of the presence of heterogeneity. Conclusions:The present study suggested that genetically determined circulating CRP showed an increased risk of developing asthma and obesity related asthma, without causality with allergic asthma.