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	Since this article does not have an abstract, we have provided the first 150 words of the full text and any section headings.

In Reply: Numerous studies have demonstrated an association between CRP levels and CVD events, including the Cardiovascular Health Study (CHS).¹ Our goal was to confirm the association between CRP polymorphisms and CRP levels and to assess whether CRP polymorphisms are associated with increased risk of incident CVD.

As noted by Dr Lawlor and colleagues, mendelian randomization methods have the potential to tease out causal effects and differentiate these effects from associations due to confounding or "reverse causation." However, the validity and utility of the mendelian randomization approach depends on a number of factors, including correct specification of the causal model and a strong association between genotype and intermediate phenotype (in this case, plasma CRP level).² The causal model for CRP is likely to be complex. C-reactive protein may be both a marker and a mediator of CVD.³ Moreover, despite the accumulating evidence for a robust association between CRP genotypes and . . . [Full Text of this Article]

Leslie A. Lange, PhD
leslie_lange@med.unc.edu

Ethan M. Lange, PhD
University of North Carolina
Chapel Hill

Russell P. Tracy, PhD
University of Vermont College of Medicine
Burlington

Alexander P. Reine, MD, MSc
University of Washington
Seattle

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