The epigenome is considered by some as the key missing piece to understanding the etiology of many biomedical diseases (Mill & Heijmans, Nat Rev Gen 2013). Epigenetic modifications are non-sequence based alterations to DNA that can induce stable changes in the regulation of gene expression. Technological advances in high-throughput DNA analysis have facilitated genome-wide examination of epigenetic modifications and large-scale association testing with disease-related outcomes. Such studies have found epigenetic markers to be associated with a variety of diseases (such as cancer and diabetes) as well as with environmental exposures (including BMI, smoking, alcohol and diet) (Relton & Davey Smith, PLoS Med 2010). Furthermore, epigenetic variation can contribute to the development of a disease or be a consequence of it. Although distinguishing the direction of causation represents a major challenge for epigenetic studies, epigenome-wide association studies (EWAS) can contribute novel molecular insights into the genetic and environmental determinants of disease-related phenotypes (Relton & Davey Smith).

We propose to conduct an EWAS exploring epigenetic markers associated with fatty acids (FAs). Polyunsaturated FAs are involved in key biological processes, including inflammatory responses, gene expression and cellular fluidity (Nakamura et al. Ann Rev Nutr 2004). Omega-3 and Omega-6 are the two main classes of polyunsaturated FAs and imbalance in the ratio of omega-6 to Omega-3 FAs and/or deficiency in omega-3 FA has been associated with adverse outcomes such as cardiovascular disease and diabetes (Yashodhara et al. J Postgrad Med 2009). Assessing epigenomic variation related to FAs may uncover novel biological insights into the role of FAs in health and disease.

Additionally we would like to utilize SNPs either related to fatty acids or methylation, to perform bidirectional MR analyses to tease out any possible causal relationships underlying methylation-fatty acid associations.