Epigenome-wide association study of serum folate in maternal peripheral blood leukocytes

Aim To perform an epigenome-wide association study (EWAS) of serum folate in maternal blood. Methods We performed cross-ancestry (Europeans=302, South Asians=161) and ancestry-specific EWAS in the EPIPREG cohort, followed by methyl quantitative trait loci (mQTL) analysis and association with cardiometabolic phenotypes. We attempted replication using folate intake estimated from a food frequency questionnaire and maternal blood methylation data from MoBa, and in a previous published EWAS of maternal serum folate in cord blood. Results cg19888088 (cross-ancestry) in EBF3 , cg01952260 (Europeans), and cg07077240 (South Asians) in HERC3 were associated with serum folate. cg19888088 and cg01952260 were associated with diastolic blood pressure. cg07077240 was associated with variants in CASC15 . The findings were not replicated in the independent samples. Conclusion Serum folate was associated with methylation at three CpG sites.