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Collaborative pooled analysis of data on C-reactive protein gene variants and coronary disease: judging causality by Mendelian randomisation

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Abstract

Many prospective studies have reported associations between circulating C-reactive protein (CRP) levels and risk of coronary heart disease (CHD), but causality remains uncertain. Studies of CHD are being conducted that involve measurement of common polymorphisms of the CRP gene known to be associated with circulating concentrations, thereby utilising these variants as proxies for circulating CRP levels. By analysing data from several studies examining the association between relevant CRP polymorphisms and CHD risk, the present collaboration will undertake a Mendelian randomisation analysis to help assess the likelihood of any causal relevance of CRP levels to CHD risk. A central database is being established containing individual data on CRP polymorphisms, circulating CRP levels, and major coronary outcomes as well as age, sex and other relevant characteristics. Associations between CRP polymorphisms or haplotypes and CHD will be evaluated under different circumstances. This collaboration comprises, at present, about 37,000 CHD outcomes and about 120,000 controls, which should yield suitably precise findings to help judge causality. This work should advance understanding of the relevance of low-grade inflammation to CHD and indicate whether or not CRP itself is involved in long-term pathogenesis.

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Abbreviations

ERFC:

Emerging Risk Factors Collaboration

CRP:

C-reactive protein

CHD:

Coronary heart disease

MI:

Myocardial infarction

SNP:

Single nucleotide polymorphism

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    CRP CHD Genetics Collaboration

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    Authors/Collaborators are listed at the end of this manuscript.

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    Supplemental Table 1

    Provisional list of studies collaborating in the CRP-Coronary Disease Genetics Collaboration as of April 2008 (DOC 220 KB)

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    CRP CHD Genetics Collaboration. Collaborative pooled analysis of data on C-reactive protein gene variants and coronary disease: judging causality by Mendelian randomisation. Eur J Epidemiol 23, 531–540 (2008). https://doi.org/10.1007/s10654-008-9249-z

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