its functional effect by altering transcription levels of that gene, which downstream subsequently predisposes to disease. Using a similar rationale, the absence of genetic association can also be informative in providing evidence against biological intermediates playing a role in disease aetiology so long as the study is adequately powered. For example, Mendelian Randomization [5] studies have shown that variants within the CRP gene appear to be unrelated to hypertension, type 2 diabetes and coronary heart disease, suggesting that CRP is unlikely to be important in the aetiology of these conditions, but rather that observational associations between CRP and these diseases are more likely to represent confounding and/or reverse causation [6]–[8].
