Table 4.
Overlapping differentially methylated regions (DMRs) in peripheral blood mononuclear cells at 9 years in relation to maternal urinary As (GW 8, ln-transformed) and plasma IGFBP3 concentrations at 9 years
| Overlap | Prenatal As | IGFBP3 | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chr | Gene symbol | Gene name | Start | End | L | p value | Dir. | Start | End | L | p value | Dir. |
| All | ||||||||||||
| 5 | MIR886 (VTRNA2-1) | Vault RNA 2-1 | 135,415,693 | 135,416,613 | 16 | 0.001 | + | 135,415,693 | 135,416,613 | 16 | 0.004 | + |
| 17 | SLFN12 | Schlafen family member 12 | 33,759,484 | 33,760,419 | 12 | 0.002 | + | 33,759,484 | 33,760,293 | 11 | 0.007 | − |
| 16 | ABAT | 4-aminobutyrate aminotransferase | 8,806,531 | 8,807,018 | 10 | 0.010 | − | 8,806,531 | 8,806,966 | 8 | 0.037 | − |
| 5 | NA | NA | 1,867,978 | 1,868,639 | 5 | 0.026 | + | 1,867,978 | 1,868,738 | 7 | 0.005 | + |
| 11 | NA | NA | 67,383,377 | 67,383,862 | 7 | 0.040 | + | 67,383,377 | 67,384,040 | 8 | 0.005 | + |
| 1 | OR2L13 | Olfactory receptor family 2 subfamily L member 13 | 248,100,345 | 248,100,614 | 7 | 0.015 | − | 248,100,228 | 248,100,614 | 9 | 0.002 | + |
| 17 | LOC728392 | NA | 5,402,972 | 5,403,516 | 5 | 0.026 | − | 5,403,053 | 5,403,516 | 4 | 0.015 | + |
| 19 | AURKC | Aurora kinase C | 57,742,217 | 57,742,444 | 8 | 0.028 | + | 57,742,112 | 57,742,444 | 9 | 0.024 | − |
| 11 | LDHC | Lactate dehydrogenase C | 18,433,564 | 18,433,887 | 5 | 0.031 | − | 18,433,500 | 18,433,745 | 6 | 0.001 | + |
| 1 | S100A13 | S100 calcium-binding protein A13 | 153,599,671 | 153,600,156 | 6 | 0.037 | + | 153,599,479 | 153,600,156 | 8 | 0.010 | + |
| Boys | ||||||||||||
| 5 | MIR886 (VTRNA2-1) | Vault RNA 2-1 | 135,415,693 | 135,416,613 | 16 | 0.000 | + | 135,415,693 | 135,416,613 | 16 | 0.003 | + |
| X |
NDUFB11
RBM10 |
NADH:Ubiquinone oxidoreductase subunit B11 RNA-binding motif protein 10 |
47,004,051 | 47,005,131 | 18 | 0.006 | + | 47,004,051 | 47,005,131 | 18 | 0.005 | + |
| X | IKBKG | Inhibitor of nuclear factor kappa B kinase subunit gamma | 153,775,262 | 153,776,009 | 16 | 0.010 | + | 153,775,262 | 153,776,009 | 16 | 0.007 | + |
| 17 | SLFN12 | Schlafen family member 12 | 33,759,484 | 33,760,419 | 12 | 0.013 | + | 33,759,484 | 33,760,293 | 11 | 0.013 | − |
| X | RNF113A | Ring finger protein 113A | 119,005,413 | 119,006,122 | 14 | 0.015 | + | 119,005,413 | 119,006,122 | 14 | 0.008 | + |
| X | ZNF674 | Zinc finger protein 674 | 46,404,528 | 46,405,125 | 14 | 0.015 | + | 46,404,528 | 46,405,125 | 14 | 0.010 | + |
| X | UPF3B | Regulator of nonsense mediated MRNA decay | 118,986,897 | 118,987,328 | 13 | 0.019 | + | 118,986,703 | 118,987,328 | 14 | 0.009 | + |
| X | LOC100272228 | NA | 149,106,454 | 149,107,029 | 13 | 0.021 | + | 149,106,022 | 149,107,029 | 15 | 0.010 | + |
| X |
TAZ
DNASE1L1 |
Tafazzin Deoxyribonuclease 1 like 1 |
153,639,778 | 153,640,967 | 12 | 0.026 | + | 153,639,778 | 153,640,967 | 12 | 0.013 | + |
| X | HMGB3 | High mobility group box 3 | 150,151,580 | 150,151,823 | 11 | 0.029 | + | 150,151,572 | 150,151,823 | 12 | 0.016 | + |
| X | RPL36A | Ribosomal protein L36a | 100,645,695 | 100,646,162 | 11 | 0.037 | + | 100,645,695 | 100,646,162 | 11 | 0.020 | + |
| X | FAM104B | Family with sequence similarity 104 member B | 55,187,242 | 55,187,903 | 11 | 0.037 | + | 55,187,242 | 55,187,903 | 11 | 0.017 | + |
| X | CLCN5 | Chloride voltage-gated channel 5 | 49,687,028 | 49,687,610 | 11 | 0.037 | + | 49,687,028 | 49,687,822 | 13 | 0.011 | + |
| X | PGK1 | Phosphoglycerate kinase 1 | 77,359,355 | 77,359,749 | 11 | 0.039 | + | 77,359,355 | 77,359,924 | 13 | 0.013 | + |
| X | ACSL4 | Acyl-CoA synthetase long chain family member 4 | 108,976,035 | 108,976,893 | 10 | 0.039 | + | 108,976,035 | 108,976,893 | 10 | 0.019 | + |
| X |
NUP62CL
CXorf41 (PIH1D3) |
Nucleoporin 62 C-terminal like PIH1 domain containing 3 |
106,449,457 | 106,449,904 | 11 | 0.040 | + | 106,449,457 | 106,449,944 | 12 | 0.018 | + |
| X | YIPF6 | Yip1 domain family member 6 | 67,718,299 | 67,719,066 | 11 | 0.041 | + | 67,718,299 | 67,719,066 | 11 | 0.018 | + |
| X | MSL3 | MSL complex subunit 3 | 11,776,256 | 11,776,935 | 8 | 0.041 | + | 11,776,256 | 11,776,935 | 8 | 0.024 | + |
| X |
ZNF182
SPACA5 |
Zinc finger protein 182 Sperm acrosome associated 5 |
47,862,977 | 47,863,707 | 11 | 0.042 | + | 47,862,977 | 47,863,707 | 11 | 0.027 | + |
| X | KIF4A | Kinesin family member 4A | 69,509,686 | 69,510,172 | 11 | 0.042 | + | 69,509,542 | 69,510,172 | 12 | 0.016 | + |
| X | ATP6AP1 | ATPase H + transporting accessory protein 1 | 153,656,771 | 153,657,411 | 9 | 0.044 | + | 153,656,771 | 153,657,411 | 9 | 0.021 | + |
| X | SYP | Synaptophysin | 49,056,505 | 49,056,886 | 10 | 0.044 | + | 49,056,505 | 49,057,013 | 11 | 0.019 | + |
| X | TSPYL2 | Testis-specific protein Y-encoded like 2 | 53,111,116 | 53,112,003 | 10 | 0.044 | + | 53,111,116 | 53,112,003 | 10 | 0.025 | + |
| X | EDA | Ectodysplasin A | 68,835,678 | 68,836,202 | 10 | 0.044 | + | 68,835,729 | 68,836,202 | 9 | 0.028 | + |
| X | PPP1R3F | Protein phosphatase 1 regulatory subunit 3F | 49,126,087 | 49,126,486 | 9 | 0.046 | + | 49,126,087 | 49,126,486 | 9 | 0.024 | + |
| X | LONRF3 | LON peptidase N-terminal domain and ring finger 3 | 118,108,506 | 118,109,413 | 10 | 0.047 | + | 118,108,506 | 118,109,413 | 10 | 0.028 | + |
| Girls | ||||||||||||
| X | HTATSF1 | HIV-1 tat specific factor 1 | 135,578,793 | 135,579,487 | 13 | 0.018 | + | 135,578,793 | 135,580,181 | 19 | 0.002 | + |
| 6 | NA | NA | 31,650,735 | 31,651,094 | 14 | 0.010 | + | 31,650,735 | 31,651,029 | 11 | 0.029 | + |
| 1 | NA | NA | 152,161,237 | 152,162,025 | 7 | 0.016 | − | 152,161,237 | 152,162,025 | 7 | 0.027 | − |
| 5 | RUFY1 | RUN and FYVE domain containing 1 | 178,986,131 | 178,986,906 | 9 | 0.035 | + | 178,986,291 | 178,986,906 | 8 | 0.049 | + |
| X | XIAP | X-linked inhibitor of apoptosis | 122,993,695 | 122,994,071 | 11 | 0.032 | + | 122,993,419 | 122,994,071 | 13 | 0.005 | + |
The overlapping DMRs refer to both complete (same start and end site) and partial (different start and/or end site) overlaps. Start, end are chromosomal coordinates according to genome built 37; Dir. refers to the direction of association with prenatal As or IGFBP3 concentrations; L, the number of CpG sites within the DMR. Cytogenic band enrichment analysis for the genes corresponding to the overlapping DMRs in boys indicated significant enrichment (FDR-adjusted p value < 0.05) for chromosome X in Xp11.23 (CLCN5, SPACA5, SYP, PPP1R3F), Xq28 (DNASE1L1, HMGB3, ATP6AP1, IKBKG) and Xq24 (UPF3B, RNF113A, LONRF3)