Table 3.
Prioritized CpGs (n = 7) with differential methylation in cord blood in relation to newborn circulating vitamin B12 concentrations sampled in cord blood at birth.1.
| CpG | Chromosome | Gene (UCSC RefGene) |
Gene location (UCSC RefGene) |
Flagged | Coefficient | Standard error | P-value | FDR-corrected P-value |
I2 | Persistence childhood | Overlap with folate hits in previous study 5 | Overlap with birth weight hits in previous study 6 | Overlap with gestational age hits in previous study 7 | Overlap with overall cognitive skills hits in previous study 8 | Overlap with nonverbal IQ hits in previous study 8 | eQTM |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| cg13863764 | 1 | PTCHD2 | Body | N | −0.94 | 0.18 | 1.12 × 10−7 | 2.96 × 10−2 | 0 | Y3,4 | N | N | N | N | N | N |
| cg00658405 | 19 | ADAMTSL5 | Body | N | 0.81 | 0.16 | 2.79 × 10−7 | 2.96 × 10−2 | 0 | N | N | N | N | N | N | N |
| cg082436192 | 1 | PTCHD2 | Body | N | −1.09 | 0.21 | 2.85 × 10−7 | 2.96 × 10−2 | 10.2 | Y | N | N | N | Y | Y | N |
| cg24371425 | 1 | PTCHD2 | Body | N | −1.03 | 0.21 | 9.36 × 10−7 | 4.64 × 10−2 | 0 | Y3 | N | Y | N | Y | N | N |
| cg02615136 | 3 | ARIH2 | Body | N | −0.26 | 0.05 | 9.93 × 10−7 | 4.64 × 10−2 | 0 | N | N | N | N | N | N | N |
| cg04096723 | 1 | RERE | N | −0.28 | 0.06 | 1.09 × 10−6 | 4.64 × 10−2 | 0 | N | N | N | N | N | N | N | |
| cg09573658 | 1 | PTCHD2 | Body | N | −0.75 | 0.15 | 1.12 × 10−6 | 4.64 × 10−2 | 43.4 | Y3 | N | N | N | N | N | N |
Abbreviations: B12, vitamin B12; eQTM: cis-expression quantitative trait methylation; CpG, cytosine-phosphate-guanine site; FDR, false discovery rate; UCSC RefGene, University of California Santa Cruz Reference Gene, SDS, standard deviation score.
1. Coefficients and standard errors represent the percentage change in DNA methylation per SDS increase in vitamin B12. One SDS vitamin B12 corresponded to a weighed mean of 171.2 pmol/L. The prioritized CpGs included those CpGs with FDR-corrected P-value<0.05 and little evidence for heterogeneity (I2 < 50%).
2. In bold, the CpG with the largest effect size.
3. Bonferroni significant in childhood look-up (P-value<0.05/7 tests; i.e., P-value<0.007).
4. Bonferroni-significant in childhood look-up, in both early and late childhood (P-value<0.05/7 tests; i.e., P-value<0.007). No persistence of newborn vitamin B12-related methylation was observed into adolescence at this significance level.
5. Look-up in results of meta-analysis of circulating folate concentrations during pregnancy and epigenome-wide cord blood DNA methylation (13).
6. Look-up in results of meta-analysis of birth weight and epigenome-wide cord blood DNA methylation (35).
7. Look-up in results of meta-analysis of gestational age and epigenome-wide cord blood DNA methylation (36).
8. Look-up in results of meta-analyses of overall cognitive skills and nonverbal IQ and epigenome-wide cord blood DNA methylation (37).