None of the other CpG sites was associated with the expression of nearby CAD-related genes. The lack of an association does not necessarily mean that methylation of these sites has no effect on expression but could result from an insufficient statistical power. This also applies for the non-significant mediation analysis. Furthermore, mRNA expression is tissue specific and an association may therefore not be found in whole blood. In addition, not all methylation sites in the human genome have an effect on mRNA expression. It could be that these methylation sites function through histone modification or DNA stability which could not be studied in the current work. Finally, it could be that these sites are merely biomarkers of tobacco smoking [5].
