Table 3:
The top 10 significant DMRs in paternal sperm associated with (a) PM2.5, (b) PM10, (c) NO2, and (d) O3
| Genomic location | FWER P-value | Symbol | Genic location | Distance | DeltaM | Function |
|---|---|---|---|---|---|---|
| (a) Top 10 PM2.5-associated DMRs | ||||||
| chr10:131213419-131215806 | 0.0001 | MGMT | Upstream | 49 647 | −0.075 | Involved in DNA repair of methylated nucleobases |
| chr1:246058026-246059550 | 0.0003 | SMYD3 | Inside intron | 521 160 | 0.143 | Histone methyltransferase (H3K4me2/3). Functions as a transcriptional activator |
| chr7:39072060-39074436 | 0.0004 | POU6F2 | Inside intron | 54 452 | −0.146 | Probable transcription factor likely to be involved in early steps in the differentiation of amacrine and ganglion cells |
| chr21:31399849-31400846 | 0.0004 | GRIK1 | Upstream | 87 568 | −0.208 | Ionotropic glutamate receptor (excitatory neurotransmitter receptor) |
| chr12:130669848-130671949 | 0.0005 | FZD10 | Downstream | 22 817 | −0.115 | Member of the frizzled gene family. Wnt protein receptor |
| chr1:234905850-234907810 | 0.0011 | IRF2BP2 | Upstream | 160 580 | −0.159 | Encodes an interferon regulatory factor-2 (IRF2) binding protein that interacts with the C-terminal transcriptional repression domain of IRF2 |
| chrX:68382003-68383827 | 0.0012 | PJA1 | Overlaps exon upstream | 1444 | −0.154 | Has E2-dependent E3 ubiquitin-protein ligase activity |
| chr12:117296502-117298878 | 0.0013 | HRK | Downstream | 20 353 | −0.069 | Member of the BCL-2 protein family. Members of this family are involved in activating apoptosis |
| chr2:3011215-3013080 | 0.0021 | TSSC1/EIPR1 | Downstream | 368 572 | −0.071 | Component of endosomal retrieval machinery involved in the trans-Golgi network for protein recycling. Located in the imprinted gene domain 11p15.5 |
| chr2:68132210-68133404 | 0.0023 | C1D | Downstream | 156 754 | −0.128 | DNA-binding and apoptosis-inducing protein, localized in the nucleus. Rac3-interacting protein that acts as a corepressor for the thyroid hormone receptor |
| (b) Top 10 PM10-associated DMRs | ||||||
| chrX:74961420-74964310 | <0.0001 | MAGEE2 | Downstream | 40 760 | −0.117 | Tumor antigen |
| chr14:24974565-24976858 | <0.0001 | CMA1 | Overlaps 3' | 612 | −0.092 | Protease of mast cells involved in vasoactive peptide generation, extracellular matrix degradation, and regulation of gland secretion |
| chr16:7142674-7144522 | <0.0001 | A2BP1 | Inside intron | 318 865 | −0.182 | RNA-binding protein that regulates alternative splicing events |
| chr10:3057233-3058630 | <0.0001 | PFKP | Upstream | 51 121 | 0.03 | Involved in glycolysis |
| chr19:30745990-30748340 | 0.0001 | ZNF536 | Upstream | 114 987 | 0.112 | May be involved in transcriptional regulating; metal binding |
| chr5:31681937-31683165 | 0.0005 | PDZD2 | Upstream | 115 865 | 0.163 | Involved in cell adhesion and prostate tumorigenesis |
| chr8:136878647-136880446 | 0.0005 | KHDRBS3 | Downstream | 408 932 | −0.122 | RNA-binding protein that plays a role in regulating alternative splicing and influences mRNA splice site selection and exon exclusion. Can regulate alternative splicing of NRXN1-3 that functions to target neurexins to postsynaptic partners in neuroligins and leucine-rich transmembrane protein family members |
| chr13:101536306-101537485 | 0.0005 | NALCN | Downstream | 531 327 | 0.155 | Voltage-independent, nonselective cation channel which belongs to a family of voltage-gated sodium and calcium channels that regulate the resting membrane potential and excitability of neurons; expressed throughout the nervous system and conducts a persistent sodium leak current that contributes to tonic neuronal excitability |
| chr2:120011056-120012516 | 0.0007 | STEAP3 | Covers exon(s) | 29 673 | 0.06 | Oxidoreductase and iron transporter; mediates responses to p53, and promotes apoptosis |
| chr10:13868030-13869444 | 0.0007 | FRMD4A | Inside intron | 503 421 | −0.118 | Regulates the remodeling of adherens junctions and linear actin cable formation during epithelial cell polarization. Polymorphisms are associated with Alz |
| (c) Top 10 NO2-associated DMRs | ||||||
| chr7:155988735-155991583 | 0.0002 | C7orf4 | Upstream | 341 601 | −0.177 | RNA gene is affiliated with the lncRNA class |
| chr4:89679783-89681417 | 0.0015 | FAM13A | Covers exon(s) | 62 984 | 0.128 | Predicted to enable GTPase activator activity |
| chr2:68132210-68133404 | 0.0017 | C1D | Downstream | 156 754 | −0.137 | DNA-binding and apoptosis-inducing protein, localized in the nucleus. Rac3-interacting protein that acts as a corepressor for the thyroid hormone receptor |
| chr21:31399849-31400846 | 0.0045 | GRIK1 | Upstream | 87 568 | −0.229 | Ionotropic glutamate receptor (excitatory neurotransmitter receptor) |
| chr20:34458591-34459341 | 0.0045 | PHF20 | Covers exon(s) | 98 669 | −0.095 | Methyllysine-binding protein, chromatin regulator component of the MOF histone acetyltransferase protein complex |
| chr18:73608225-73609747 | 0.0068 | ZNF516 | Downstream | 565 307 | −0.115 | Transcriptional regulator that promotes brown adipose tissue differentiation |
| chr8:4697089-4698489 | 0.0103 | CSMD1 | Inside intron | 153 838 | 0.167 | Predicted to act upstream of many processes including learning/memory and reproductive structure development |
| chr11:57639658-57641171 | 0.0109 | CTNND1 | Downstream | 110 425 | −0.148 | Armadillo protein family member involved in cell–cell adhesion |
| chr9:129642026-129643484 | 0.0109 | ZBTB34 | Inside exon | 19 083 | −0.146 | Predicted to enable DNA-binding transcription repressor activity |
| chr12:77965737-77966649 | 0.0112 | NAV3 | Upstream | 258 419 | −0.294 | Part of the neuron navigator family of proteins that is predominantly expressed in the nervous system |
| (d) Top 10 O3-associated DMRs | ||||||
| chr11:57639658-57641253 | <0.0001 | CTNND1 | Downstream | 110 425 | 0.308 | Armadillo protein family member involved in cell–cell adhesion |
| chr13:40976148-40978047 | <0.0001 | LOC646982 | Inside intron | 77 095 | 0.218 | Long noncoding RNA |
| chr9:20267374-20268174 | 0.0004 | MLLT3 | Downstream | 354 339 | 0.377 | chromatin reader component of the super elongation complex that increases the catalytic rate of RNA pol II txn |
| chr7:155989653-155991513 | 0.0015 | C7orf4; LINC00244 | Upstream | 341 671 | 0.077 | RNA gene is affiliated with the lncRNA class |
| chr8:3722198-3723528 | 0.0015 | CSMD1 | Inside intron | 1 128 799 | −0.201 | Predicted to act upstream of many processes including learning/memory and reproductive structure development |
| chr1:15066168-15067918 | 0.0041 | KIAA1026 | Inside intron | 140 956 | −0.124 | Gene encodes a protein that plays a role in desmosome assembly, cell adhesion, cytoskeletal organization, and epidermal differentiation |
| chr1:215843109-215844569 | 0.0042 | USH2A | Overlaps exon downstream | 752 168 | −0.108 | Involved in hearing and vision as member of the USH2 complex. Protein is found in the basement membrane and may be important in development and homeostasis of the inner ear and retina. |
| chr4:186693264-186695194 | 0.0047 | SORBS2 | Inside intron | 1871 | −0.119 | Adapter protein that plays a role in the assembling of signaling complexes, being a link between ABL kinases and actin cytoskeleton. |
| chr12:77965737-77966707 | 0.0050 | NAV3 | Upstream | 258 361 | 0.29 | This gene belongs to the neuron navigator family and is expressed predominantly in the nervous system. May regulate interleukin-2 production by T-cells. May be involved in neuron regeneration. |
| chr16:78376735-78378365 | 0.0055 | WWOX | Inside intron | 243 185 | −0.112 | Oxidoreductase involved in neuronal signaling and DNA damage repair |
The boundaries of the DMR are shown in the genomic location column; the FWER P-value is displayed alongside the gene symbol. The genic location characterized where within the gene body the DMR is located. deltaM is the difference in sperm methylation from the highest and lowest exposure quartiles. Gene functions were taken from the human protein atlas (proteinatlas.org) as well as gene cards (genecards.org).