Reply to PA Dugué et
and white blood cell proportions; and similar study design. Of note, previous analyses of blood samples fromMCCS participants showed substantial replication of previously identified signals and discovered highly replicable novel associations for other health risk factors such as BMI (7), alcohol consumption (8), and tobacco smoking (9). Taken together, our data and those presented in Mandaviya et al. would mean that there is at best weak evidence for an association between FFQ-derived intakes of folate and vitamin B-12 and DNA methylation in peripheral blood. This suggests that blood DNA methylation might not mediate, nor be a useful marker of, the association between intake of these nutrients and disease risk and shows the complexity of the one-carbon metabolism pathway in terms of, e.g., the number of nutrients involved, their interactions, and existing interindividual differences in nutrient absorption and metabolism.