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Published on: January 28, 2020

Association between C reactive protein and coronary heart disease: mendelian randomisation analysis based on

, Frances Wensley, Pei Gao

    BMJ (Clinical Research Ed.)
    |February 18, 2011
    PubMed

    Insights

    Genetic variants show C reactive protein (CRP) is unlikely to be a causal factor in coronary heart disease. Mendelian randomization meta-analysis found no significant association between genetically raised CRP and heart disease risk.

    Area of Science:

    • Cardiovascular Genetics
    • Inflammation Biomarkers
    • Epidemiology

    Background:

    • C reactive protein (CRP) is a marker of inflammation and is associated with coronary heart disease (CHD) risk.
    • The causal role of CRP in CHD remains debated, with observational studies suggesting a link.

    Purpose of the Study:

    • To investigate the causal relationship between C reactive protein concentration and coronary heart disease using genetic variants as instrumental variables.
    • To leverage Mendelian randomization to overcome confounding in observational studies.

    Main Methods:

    • A large-scale Mendelian randomization meta-analysis of individual participant data from 47 epidemiological studies.
    • Involved 194,418 participants, including 46,557 with CHD.
    • Utilized four CRP gene tagging single nucleotide polymorphisms (SNPs) as genetic proxies for CRP levels.

    Main Results:

    • The four CRP genetic variants were strongly associated with CRP concentration but not with other cardiovascular risk factors.
    • Individually, the SNPs showed no significant association with CHD risk per allele.
    • Combined analysis indicated no increased risk of CHD per standard deviation increase in genetically predicted CRP (Risk Ratio: 1.00, 95% CI: 0.90-1.13).
    • This contrasted sharply with observational data showing a significant increase in CHD risk with higher circulating CRP levels (Risk Ratio: 1.33, 95% CI: 1.23-1.43).

    Conclusions:

    • Human genetic data strongly suggest that C reactive protein concentration is unlikely to be a causal factor in coronary heart disease.
    • The association observed in epidemiological studies may be due to confounding or reverse causation.
    Abstract

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