Table 3.
Top enriched pathways (FDRenrichment < 0.005) for DNAm sites with significant associations between maternal-neonatal differences in methylation levels (ΔDNAm) and newborn sex
| Enriched pathway | Number of genes in pathway map | Number of genes in data | Enrichment analysis | |
|---|---|---|---|---|
| P | FDR | |||
| Protein folding and maturation_POMC processing | 30 | 19 | 4.2 × 10–13 | 6.1 × 10–10 |
| Tau pathology in Alzheimer disease | 55 | 21 | 6.6 × 10–9 | 3.4 × 10–6 |
| LRRK2 in neurons in Parkinson's disease | 33 | 16 | 6.8 × 10–9 | 3.4 × 10–6 |
| Development_Positive regulation of WNT/Beta-catenin signaling in the nucleus | 69 | 22 | 1.3 × 10–7 | 4.7 × 10–5 |
| Development_Positive regulation of WNT/Beta-catenin signaling in the cytoplasm | 76 | 23 | 2.0 × 10–7 | 5.8 × 10–5 |
| Neurophysiological process_Constitutive and activity-dependent synaptic AMPA receptor delivery | 59 | 19 | 7.8 × 10–7 | 0.0002 |
| Development_Hedgehog signaling | 94 | 25 | 9.0 × 10–7 | 0.0002 |
| Immune response_IL-3 signaling via ERK and PI3K | 102 | 26 | 1.3 × 10–6 | 0.0002 |
| Ligand-independent activation of Androgen receptor in Prostate Cancer | 67 | 20 | 1.5 × 10–6 | 0.0002 |
| Signal transduction_PKA signaling | 51 | 17 | 1.7 × 10–6 | 0.0002 |
| Regulation of GSK3 beta in bipolar disorder | 46 | 16 | 1.8 × 10–6 | 0.0002 |
| Cytoskeleton remodeling_Neurofilaments in axon growth and synapses | 23 | 11 | 2.0 × 10–6 | 0.0002 |
| Transcription_Negative regulation of HIF1A function | 69 | 20 | 2.6 × 10–6 | 0.0003 |
| Cytoskeleton remodeling_Regulation of actin cytoskeleton organization by the kinase effectors of Rho GTPases | 58 | 18 | 2.8 × 10–6 | 0.0003 |
| Neurophysiological process_Constitutive and regulated NMDA receptor trafficking | 65 | 19 | 4.0 × 10–6 | 0.0004 |
| Signal transduction_Adenosine A2B receptor signaling pathway | 71 | 20 | 4.2 × 10–6 | 0.0004 |
| Development_WNT/Beta-catenin signaling in the cytoplasm | 55 | 17 | 5.5 × 10–6 | 0.0005 |
| Role of tumor-infiltrating B cells in anti-tumor immunity | 91 | 23 | 6.2 × 10–6 | 0.0005 |
| Development_Negative regulation of WNT/Beta-catenin signaling at the receptor level | 45 | 15 | 7.0 × 10–6 | 0.0005 |
| Neurogenesis_NGF/ TrkA MAPK-mediated signaling | 105 | 25 | 7.9 × 10–6 | 0.0006 |
| Immune response_Fc epsilon RI pathway: calcium-dependent signaling | 68 | 19 | 8.3 × 10–6 | 0.0006 |
| Signal transduction_Angiotensin II signaling via Beta-arrestin | 57 | 17 | 9.5 × 10–6 | 0.0006 |
| Neurophysiological process_Synaptic vesicle fusion and recycling in nerve terminals | 52 | 16 | 1.1 × 10–5 | 0.0007 |
| Nociception_Nociceptin receptor signaling | 76 | 20 | 1.3 × 10–5 | 0.0008 |
| Development_Negative feedback regulation of WNT/Beta-catenin signaling | 37 | 13 | 1.5 × 10–5 | 0.0009 |
| Chemotaxis_Lysophosphatidic acid signaling via GPCRs | 129 | 28 | 1.5 × 10–5 | 0.0009 |
| Development_WNT/Beta-catenin signaling pathway. Signalosome | 43 | 14 | 1.9 × 10–5 | 0.0010 |
| Development_PTHR1 in bone and cartilage development | 78 | 20 | 2.0 × 10–5 | 0.0010 |
| Immune response_Platelet activating factor/ PTAFR pathway signaling | 55 | 16 | 2.4 × 10–5 | 0.0012 |
| Development_Estrogen-independent activation of ESR1 and ESR2 | 44 | 14 | 2.6 × 10–5 | 0.0013 |
| Cell cycle progression in Prostate Cancer | 39 | 13 | 2.8 × 10–5 | 0.0014 |
| Development_WNT/Beta-catenin signaling in the nucleus | 62 | 17 | 3.2 × 10–5 | 0.0015 |
| Immune response_Fc epsilon RI pathway: Lyn-mediated cytokine production | 87 | 21 | 3.3 × 10–5 | 0.0015 |
| Development_Membrane-bound ESR1: interaction with growth factors signaling | 45 | 14 | 3.4 × 10–5 | 0.0015 |
| Altered Ca2 + handling in heart failure | 35 | 12 | 4.2 × 10–5 | 0.0018 |
| Signal transduction_Additional pathways of NF-kB activation (in the cytoplasm) | 52 | 15 | 4.9 × 10–5 | 0.0019 |
| Development_Endothelin-1/EDNRA signaling | 52 | 15 | 4.9 × 10–5 | 0.0019 |
| Signal transduction_Activation of PKC via G-Protein coupled receptor | 52 | 15 | 4.9 × 10–5 | 0.0019 |
| Cytoskeleton remodeling_Role of PKA in cytoskeleton reorganization | 41 | 13 | 5.2 × 10–5 | 0.0020 |
| NF-AT signaling in cardiac hypertrophy | 65 | 17 | 6.2 × 10–5 | 0.0023 |
| Apoptosis and survival_BAD phosphorylation | 42 | 13 | 6.9 × 10–5 | 0.0025 |
| Signal transduction_Calcium-mediated signaling | 72 | 18 | 7.3 × 10–5 | 0.0025 |
| Muscle contraction_Relaxin signaling pathway | 48 | 14 | 7.6 × 10–5 | 0.0026 |
| Cytoskeleton remodeling_Reverse signaling by Ephrin-B | 32 | 11 | 8.5 × 10–5 | 0.0029 |
| Neurophysiological process_Thyroliberin signaling | 73 | 18 | 8.8 × 10–5 | 0.0029 |
| POMC, alpha-MSH and AGRP in regulation of food intake and energy expenditure in obesity in hypothalamus | 43 | 13 | 9.0 × 10–5 | 0.0029 |
| Role of neuropeptides in pathogenesis of SCLC | 67 | 17 | 9.4 × 10–5 | 0.0029 |
| Transcription_CREB signaling pathway | 49 | 14 | 9.7 × 10–5 | 0.0030 |
| Signal transduction_Cyclic AMP signaling | 38 | 12 | 1.0 × 10–4 | 0.0031 |
| Immune response_IL-6 signaling pathway via MEK/ERK and PI3K/AKT cascades | 74 | 18 | 1.1 × 10–4 | 0.0031 |
| Cytoskeleton remodeling_CDC42 in cellular processes | 23 | 9 | 1.2 × 10–4 | 0.0034 |
| Neurophysiological process_Corticoliberin signaling via CRHR1 | 50 | 14 | 1.2 × 10–4 | 0.0034 |
| Apoptotic pathways and resistance to apoptosis in lung cancer cells | 56 | 15 | 1.2 × 10–4 | 0.0034 |
| Tinnitus-associated changes in auditory pathway | 82 | 19 | 1.4 × 10–4 | 0.0038 |
| Cell adhesion_Histamine H1 receptor signaling in the interruption of cell barrier integrity | 45 | 13 | 1.5 × 10–4 | 0.0041 |
| Ca(2 +)-dependent NF-AT signaling in cardiac hypertrophy | 57 | 15 | 1.5 × 10–4 | 0.0041 |
| Signal transduction_Erk Interactions: Inhibition of Erk | 34 | 11 | 1.6 × 10–4 | 0.0041 |
| Development_Positive regulation of WNT/Beta-catenin signaling at the receptor level | 64 | 16 | 1.8 × 10–4 | 0.0046 |
FDR, false discovery rate