Another notable finding involves the relationship between allelic scores that index CRP levels and disease. It is interesting that the genome-wide allelic score that indexed CRP correlated with many of the WTCCC diseases, whereas the allelic score constructed from the known regions only, did not. Mendelian Randomization studies have shown that CRP is unlikely to cause several diseases to which it had been linked including type II diabetes and coronary heart disease, but rather the observational associations are probably a secondary consequence of the disease itself or due to latent confounding [6]–[8]. Given that the genome-wide allelic score actually explained less variance in CRP level than the known variant score (i.e. 2% versus 5%), we suggest that a causal effect of CRP on the different diseases is unlikely, but rather that genetic pleiotropy and the lack of specificity of the genome-wide allelic score is the most likely explanation for this difference. For example, many BMI associated SNPs are present at quite low levels of significance in the CRP GWAS meta-analysis (Table S9), although in this case, not at genome-wide significant
