25-Hydroxyvitamin D in pregnancy and genome wide cord blood DNA methylation in two pregnancy cohorts (MoBa and ALSPAC).
Bottom Line: Further exploration of a set of CpG sites in the proximity of four a priori defined candidate genes (CYP24A1, CYP27B1, CYP27A1 and CYP2R1) did not result in any associations with FDR<0.05 (56 tests).In this large genome wide assessment of the potential influence of maternal vitamin D status on DNA methylation, we did not find any convincing associations in 1416 newborns.If true associations do exist, their identification might require much larger consortium studies, expanded genomic coverage, investigation of alternative cell types or measurements of 25-hydroxyvitamin D at different gestational time points.
Affiliation: MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Oakfield Grove, Clifton, Bristol BS8 2BN, UK. Electronic address: email@example.com.Show MeSH
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Mentions: There was no association between mid-pregnancy 25(OH)D and cord blood DNA methylation at any single site on the Illumina HumanMethylation450 BeadChip among the 819 mother and child-pairs in MoBa and the 597 mother and child-pairs in ALSPAC (at FDR < 0.05; 473,731 tests). Adjustment for potential confounding variables (See Table 1, as well as the Materials and Methods section) and cell-type estimations as well as a meta-analysis, based on Fisher's method, comprising results from both MoBa and ALSPAC cohorts did not result in any association between maternal 25(OH)D levels and DNA methylation in offspring (at FDR < 0.05; 473,731 tests). The 1000 strongest associations are provided in Supplementary Information file 1. Regression estimates tended to be very small, and all p-values were greater than 0.05 after correction for multiple tests (FDR > 0.2, Bonferroni adjusted p > 0.2, 473731 tests). Fig. 1 shows QQ- and volcano plots for both MoBa and ALSPAC cohorts based on coefficient estimates and p-values for 473731CpG probes. Fig. 2 shows the lack of agreement in effect sizes in MoBa and ALSPAC for the top 20 meta-analyzed associations. Information regarding maternal circulating 25(OH)D levels and other covariates used throughout the study can be found in Table 1.
Affiliation: MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Oakfield Grove, Clifton, Bristol BS8 2BN, UK. Electronic address: firstname.lastname@example.org.