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.

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