B3140 - Applying genetic risk scores for one-carbon micronutrients to Mendelian randomization and epigenome-wide association analyses - 18/07/2018
Folate and other B vitamins are one-carbon micronutrients essential for a range of biological processes such as DNA replication, repair and gene expression. Folate, for instance, plays a key role in fetal development and can significantly reduce the risk of neural tube defects (NTD). Folate is available in small quantities in many foods however it is recommended that women supplement with folic acid (synthetic form of folate) daily during pregnancy. The association between insufficient folate and NTD has led to several countries recommending the fortification of foods such as flour and cereal grains with folic acid. In addition to a putative role of maternal folate deficiency in fetal development, blood folate levels have been linked, albeit inconsistently, to risk of various cancers in population-based studies. It is believed that one mechanism through which folate may influence subsequent adverse developmental outcomes and cancer risk in early life is via differential DNA methylation (a form of gene regulation) in blood. Consequently, our proposed research aims to further interrogate an effect of one-carbon micronutrient levels on various cancer outcomes, in addition to examining whether a putative effect of one-carbon micronutrient levels on both adverse developemental outcomes and cancer may operate through epigenetic mechanisms in early life. To perform these analyses we will use genome-wide association data derived from previous analyses performed in ALSPAC (B2104) to 1) estimate the causal effect of genetically-proxied blood folate on various adult cancers (using previously published summary GWAS data for these cancers), and 2) to examine the effect of genetic risk scores for various one-carbon micronutrients on DNA methylation profiles in children.