Elevated circulating C-reactive protein (CRP) levels may raise the risk of developing idiopathic pulmonary fibrosis (IPF) in individuals of European descent, according to a study published in Respiratory Research. 

IPF, an aggressive and irreversible lung disorder that leads to early death, is driven by inflammation. Given that CRP is an inflammatory maker, scientists hypothesize that elevated CRP may have a causal relationship with IPF. 

Epidemiological studies indicate that the incidence of IPF in North America and Europe is among the highest in the world. The authors of this study hence sought to understand the association between IPF and circulating CRP levels among individuals of European ancestry, via Mendelian randomization. 

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“[Mendelian randomization] analysis is a new epidemiological approach that uses genetic variations as instrumental variables to estimate the causal relationship between exposure and outcome,” they wrote. 

Read more about IPF etiology 

The research team utilized data from a meta-analysis of 88 genome-wide association studies (GWAS) that included 204,402 individuals; this revealed 58 genome-wide significant genetic loci for circulating CRP. They also used GWAS analysis of IPF from the FinnGen Biobank, which contains the genotype data of 1028 IPF patients and 196,986 controls, as outcome variables. 

The authors of this study obtained 54 single-nucleotide polymorphisms (SNPs) as instrumental variables to assess the relationship between each SNP and IPF risk. Upon performing a Mendelian randomization analysis, they discovered a causal relationship between circulating CRP levels and the risk of developing IPF. 

This finding differs from existing studies in suggesting that CRP is not merely a marker for IPF prognosis, but that it plays a significant role in the development of IPF itself. It adds to the list of possible causes of IPF, which includes environmental pollutants, dust, and oxidative stress. 

“Further pathological and biochemical studies are needed to investigate further the profound relationship of increased risk of IPF by elevated circulating CRP levels,” the authors of the study wrote. 


Zhang K, Li A, Zhou J, Zhang C, Chen M. Genetic association of circulating C-reactive protein levels with idiopathic pulmonary fibrosis: a two-sample Mendelian randomization studyRespir Res. 2023;24(1):7. doi:10.1186/s12931-022-02309-x