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The causality between C-reactive protein and asthma: a two-sample Mendelian randomization analysis.

Yong Mou1, Wenhao Cao1, Rujuan Wang1

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Higher C-reactive protein (CRP) levels genetically increase the risk for asthma and obesity-related asthma. However, CRP does not appear to causally influence allergic asthma risk.

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Area of Science:

  • Genetics and Epidemiology
  • Respiratory Medicine
  • Inflammation Research

Background:

  • C-reactive protein (CRP) is a marker of inflammation.
  • Asthma is a chronic respiratory disease with complex etiology.
  • The causal relationship between CRP and asthma risk requires further investigation.

Purpose of the Study:

  • To investigate the potential causal effect of circulating C-reactive protein (CRP) levels on the risk of asthma and its subtypes.
  • To utilize a two-sample Mendelian randomization (MR) approach for robust causal inference.

Main Methods:

  • Employed single nucleotide polymorphisms (SNPs) associated with CRP and asthma outcomes as instrumental variables (IVs).
  • Performed Mendelian randomization analysis primarily using the inverse variance weighted (IVW) method.
  • Assessed heterogeneity and pleiotropy using Cochran's Q test and MR-Egger regression, with leave-one-out analysis for robustness.

Main Results:

  • Identified 42 SNPs as valid IVs for the MR analysis.
  • Found a significant causal association between higher CRP levels and increased risk of asthma (OR: 1.046, P=0.030) and obesity-related asthma (OR: 1.072, P=0.025).
  • No significant causal link was observed between CRP and allergic asthma (OR: 1.051, P=0.081).

Conclusions:

  • Higher circulating C-reactive protein (CRP) levels are suggested to genetically predict an elevated risk of developing asthma.
  • CRP may play a causal role specifically in obesity-related asthma.
  • The study found no evidence of a causal relationship between CRP and allergic asthma.