C-Reactive Protein and Cardiovascular Disease Risk: Still an Unknown Quantity?

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   Figure. The random allocation of alleles at conception provides a natural experiment (analogous to a randomized, controlled trial) for testing causal association of circulating C-reactive protein ( ) level with coronary heart disease ( ) outcome. Observational epidemiologic associations between circulating CRP level and CHD ( ) can be misinterpreted because of the existence of confounding, reverse causation, or bias ( ). Under the assumptions of Mendelian randomization and where robust associations between CRP genotype and circulating CRP level are present (A), the analysis of the relationship between CRP genotype and CHD (B) can help to assess the nature of the association between circulating CRP and CHD. In this case, an association between genotype and CHD would implicate causality, while a null relationship would suggest that confounding, reverse causation, or bias has generated the observed link between circulating CRP level and CHD. Mendelian randomization.CRPCHDdotted linedashed line