Table 2.
Differentially methylated regions (DMRs) of epigenome-wide associations between log2-transformed toenail arsenic concentrations (mother’s or father’s; μg/g) and DNA methylation levels (M-values) in dural tissue, whole blood, or buccal swab samples from infants with spina bifida, adjusting for infant age at collection (days), infant sex, maternal serum folate levels (ng/mL), and surrogate variables.
| Arsenic Exposure | DNA Methylation | Chr | Start | End | Sidak p | # of Probes | Genes | Average Regression Coefficienta |
|---|---|---|---|---|---|---|---|---|
| Maternal | Dural Tissue | |||||||
| 4 | 99,850,885 | 99,851,282 | 5.3E-06 | 8 | EIF4E | −0.31 | ||
| 8 | 144,654,887 | 144,655,169 | 5.3E-04 | 5 | C8orf73, MROH6 | −0.29 | ||
| 11 | 8,931,473 | 8,931,709 | 3.8E-06 | 4 | AKIP1, ST5, C11orf17 | −0.35 | ||
| 12 | 11,708,829 | 11,709,052 | 1.0E-03 | 3 | LINC01252 | 0.24 | ||
| 16 | 86,994,949 | 86,995,082 | 5.1E-04 | 3 | −0.20 | |||
| 17 | 48,042,779 | 48,043,064 | 9.0E-04 | 4 | 0.32 | |||
| 18 | 55,862,468 | 55,862,873 | 1.0E-03 | 7 | NEDD4L | 0.18 | ||
| 19 | 45,449,006 | 45,449,166 | 6.5E-03 | 5 | APOC2, APOC4-APOC2 | 0.17 | ||
| 20 | 62,327,968 | 62,328,095 | 1.1E-03 | 4 | TNFRSF6B, RTEL1-TNFRSF6B | −0.36 | ||
| Paternal | Dural Tissue | |||||||
| 2 | 241,564,613 | 241,564,828 | 4.7E-04 | 4 | GPR35 | −0.19 | ||
| 8 | 144,654,887 | 144,655,261 | 1.6E-12 | 6 | C8orf73, MROH6 | −0.31 | ||
| 8 | 144,659,831 | 144,659,884 | 8.6E-03 | 2 | NAPRT1 | −0.40 | ||
| Maternal | Whole Blood | |||||||
| 1 | 116,021,925 | 116,022,092 | 4.4E-03 | 3 | −0.11 | |||
| 1 | 174,843,523 | 174,843,972 | 4.0E-10 | 7 | RABGAP1L | −0.10 | ||
| 1 | 209,897,614 | 209,897,838 | 3.9E-03 | 3 | HSD11B1 | 0.07 | ||
| 2 | 10,571,959 | 10,572,110 | 4.9E-04 | 2 | −0.25 | |||
| 2 | 242,702,749 | 242,702,933 | 4.4E-03 | 3 | D2HGDH | −0.10 | ||
| 4 | 1,166,767 | 1,167,070 | 6.4E-05 | 8 | LOC100130872-SPON2, SPON2 | −0.07 | ||
| 4 | 153,099,743 | 153,099,834 | 3.7E-03 | 3 | 0.08 | |||
| 6 | 33,280,149 | 33,280,401 | 3.2E-02 | 7 | TAPBP | −0.08 | ||
| 6 | 33,282,736 | 33,283,294 | 2.7E-12 | 23 | ZBTB22, TAPBP | −0.08 | ||
| 10 | 81,904,244 | 81,904,332 | 4.7E-03 | 2 | PLAC9 | −0.22 | ||
| 10 | 101,825,029 | 101,825,186 | 1.8E-03 | 4 | CPN1 | −0.10 | ||
| 12 | 54,446,019 | 54,446,577 | 7.3E-09 | 10 | HOXC4 | 0.19 | ||
| 16 | 8,806,359 | 8,807,012 | 0.0E + 00 | 11 | ABAT | −0.25 | ||
| 18 | 10,862 | 11,156 | 3.1E-03 | 8 | LOC102723376 | −0.13 | ||
| 19 | 719,323 | 719,633 | 1.9E-04 | 3 | PALM | −0.15 | ||
| 19 | 45,449,006 | 45,449,166 | 4.4E-03 | 5 | APOC2, APOC4-APOC2 | 0.16 | ||
| 19 | 49,522,817 | 49,523,047 | 2.9E-04 | 3 | −0.37 | |||
| 20 | 43,935,222 | 43,935,552 | 4.5E-09 | 10 | MATN4, RBPJL | −0.14 | ||
| 20 | 45,179,226 | 45,179,414 | 1.7E-04 | 5 | C20orf123, OCSTAMP | 0.08 | ||
| Paternal | Whole Blood | |||||||
| 1 | 174,843,523 | 174,843,768 | 1.2E-05 | 5 | RABGAP1L | −0.10 | ||
| 1 | 228,361,582 | 228,361,642 | 1.2E-02 | 2 | C1orf69, IBA57 | −0.26 | ||
| 3 | 113,417,803 | 113,418,005 | 1.3E-03 | 3 | −0.10 | |||
| 6 | 33,282,736 | 33,283,294 | 1.1E-10 | 23 | ZBTB22, TAPBP | −0.09 | ||
| 6 | 33,560,953 | 33,561,450 | 3.3E-03 | 8 | C6orf227 | −0.23 | ||
| 6 | 76,203,225 | 76,203,676 | 7.3E-09 | 7 | FILIP1 | 0.18 | ||
| 9 | 114,557,226 | 114,557,447 | 1.5E-04 | 4 | C9orf84 | −0.19 | ||
| 10 | 4,868,328 | 4,868,399 | 7.7E-03 | 6 | AKR1E2 | 0.19 | ||
| 10 | 72,219,713 | 72,219,820 | 7.4E-04 | 3 | −0.16 | |||
| 12 | 54,413,101 | 54,413,559 | 9.3E-06 | 5 | HOXC6, HOXC5, HOXC4 | 0.12 | ||
| 12 | 54,446,019 | 54,446,577 | 5.5E-10 | 10 | HOXC4 | 0.23 | ||
| 14 | 54,418,728 | 54,418,881 | 7.7E-04 | 4 | BMP4 | 0.15 | ||
| 16 | 8,806,359 | 8,807,012 | 0.0E + 00 | 11 | ABAT | −0.28 | ||
| 19 | 7,983,877 | 7,984,172 | 1.1E-05 | 5 | SNAPC2 | −0.18 | ||
| 19 | 49,522,817 | 49,523,047 | 1.2E-05 | 3 | −0.42 | |||
| 20 | 45,179,226 | 45,179,414 | 4.2E-03 | 5 | C20orf123, OCSTAMP | 0.09 | ||
| Maternal | Buccal Swab | |||||||
| 6 | 33,288,180 | 33,288,636 | 1.9E-06 | 8 | DAXX | −0.16 | ||
| 13 | 114,138,225 | 114,138,358 | 2.6E-02 | 4 | DCUN1D2 | −0.16 | ||
| 16 | 2,879,998 | 2,880,168 | 1.1E-05 | 3 | ZG16B | −0.21 | ||
| 18 | 10,862 | 11,156 | 3.4E-05 | 8 | LOC102723376 | −0.16 | ||
| Paternal | Buccal Swab | |||||||
| 1 | 228,362,309 | 228,362,510 | 5.8E-04 | 3 | C1orf69 | −0.72 | ||
| 8 | 6,481,431 | 6,481,609 | 3.8E-05 | 3 | MCPH1, MCPH1-AS1 | −0.27 | ||
| 14 | 37,126,582 | 37,126,903 | 3.6E-07 | 4 | PAX9 | −0.43 | ||
| 15 | 86,313,834 | 86,313,974 | 2.1E-06 | 7 | MIR1276, KLHL25 | 0.19 | ||
| 21 | 46,654,108 | 46,654,236 | 1.7E-06 | 3 | −0.22 |
Abbreviations: chr, chromosome.
aThe average regression coefficient on the M-value scale was calculated by extracting the EWAS coefficients for each CpG site included in a DMR and then averaging the values across the CpG sites.