Aim: Homocysteine (Hcy) is a sensitive marker of one-carbon metabolism. Higher Hcy levels have been associated with global DNA hypomethylation. We investigated the association between plasma Hcy and epigenome-wide DNA methylation in leukocytes. Methods: Methylation was measured using Illumina 450 k arrays in 2035 individuals from six cohorts. Hcy-associated differentially methylated positions and regions were identified using meta-analysis. Results: Three differentially methylated positions cg21607669 (SLC27A1), cg26382848 (AJUBA) and cg10701000 (KCNMA1) at chromosome 19, 14 and 10, respectively, were significantly associated with Hcy. In addition, we identified 68 Hcy-associated differentially methylated regions, the most significant of which was a 1.8-kb spanning domain (TNXB/ATF6B) at chromosome 6. Conclusion: We identified novel epigenetic loci associated with Hcy levels, of which specific role needs to be further validated.

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Keywords 450 k array, association, DMP, DMR, DNA methylation, epigenome-wide analysis, homocysteine, meta-analysis
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Journal Epigenomics
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Mandaviya, P.R, Aïssi, D. (Dylan), Dekkers, K.F. (Koen F), Joehanes, R, Kasela, S, Truong, V, … Heil, S.G. (2017). Homocysteine levels associate with subtle changes in leukocyte DNA methylation: An epigenome-wide analysis. Epigenomics, 9(11), 1403–1422. doi:10.2217/epi-2017-0038