Appendix 2.
Gene Set Overrepresentation Results for Diseases, OMIM and GLAD4U, from Illumina-Normalized Methylation Models
| Gene Set | Description | Size | Expect | Ratio | P Value | FDR |
|---|---|---|---|---|---|---|
| GLAD4U Database | ||||||
| PA445752 | Stress | 616 | 506.36 | 1.13 | 3.8E–14 | 1.1E–10 |
| PA445092 | Nervous System Malformations | 260 | 213.72 | 1.15 | 7.3E–09 | 1.0E–05 |
| PA445914 | Translocation, Genetic | 504 | 414.29 | 1.11 | 1.7E–08 | 1.6E–05 |
| PA443275 | Adhesion | 711 | 584.45 | 1.09 | 4.9E–08 | 3.4E–05 |
| PA446836 | Craniofacial Abnormalities | 313 | 257.29 | 1.13 | 5.9E–08 | 3.4E–05 |
| PA445000 | Musculoskeletal Abnormalities | 353 | 290.17 | 1.11 | 3.9E–07 | 1.9E–04 |
| PA447208 | Mental Disorders | 637 | 523.62 | 1.08 | 1.5E–06 | 6.0C–04 |
| PA4434S4 | Ataxia | 291 | 239.20 | 1.11 | S.3E–06 | 1.8E–03 |
| PA44616S | Leukemia, T-Cell | 202 | 166.05 | 1.13 | S.7E–06 | 1.8E–03 |
| PA444944 | Microcephaly | 145 | 119.19 | 1.15 | 1.1E–05 | 3.1E–03 |
| PA4436S3 | Cell Transformation, Neoplastic | 326 | 267.97 | 1.10 | 1.6E–05 | 4.1E–03 |
| PA445100 | Neuroblastoma | 229 | 188.24 | 1.12 | 3.0E–05 | 6.6E–03 |
| PA447278 | Depression | 221 | 181.66 | 1.12 | 3.0E–05 | 6.6E–03 |
| PA4434S2 | Astigmatism | 52 | 42.74 | 1.22 | 3.7E–05 | 7.5E–03 |
| PA444750 | Leukemia | 482 | 396.21 | 1.08 | S.8E–05 | LIE–02 |
| PA445644 | Shock | 340 | 279.48 | 1.09 | 6.9E–05 | 1.2E–02 |
| PA444833 | Lymphatic Diseases | 379 | 311.54 | 1.08 | 9.5E–05 | 1.5E–02 |
| PA166114377 | Hand-foot syndrome | 60 | 49.32 | 1.20 | 1.1E–04 | 1.5E–02 |
| PA444756 | Leukemia, Lymphoid | 292 | 240.03 | 1.10 | 1.1E–04 | 1.5E–02 |
| PA165108377 | Lymphoid leukemia NOS | 292 | 240.03 | 1.10 | 1.1E–04 | 1.5E–02 |
| PA444340 | Lymphoma | 363 | 298.39 | 1.09 | 1.1E–04 | 1.5E–02 |
| PA165108622 | Drug interaction with drug | 480 | 394.56 | 1.07 | 1.2E–04 | 1–5E–02 |
| PA4434SS | Ataxia Telangiectasia | 185 | 152.07 | 1.12 | 1.3E–04 | 1.6E–02 |
| PA443963 | Dysostoses | 100 | 82.20 | 1.16 | 1.4E–04 | 1.6E–02 |
| PA165108317 | Developmental disorder NOS | 133 | 109.33 | 1.13 | 1.9E–04 | 2.2E–02 |
| PA443842 | Death | 397 | 326.34 | 1.08 | 2.2E–04 | 2.4E–02 |
| PA445538 | Retinoblastoma | 216 | 177.55 | 1.10 | 2.8E–04 | 2.7E–02 |
| PA446858 | Neurodegenerative Diseases | 441 | 362.51 | 1.07 | 2.9E–04 | 2.7E–02 |
| PA447230 | HIV | 826 | 678.98 | 1.05 | 3.0E–04 | 2.7E–02 |
| PA446859 | Loss of Heterozygosity | 245 | 201.39 | 1.10 | 3.0E–04 | 2.7E–02 |
| PA443269 | Adenoma | 185 | 152.07 | 1.11 | 3.1E–04 | 2.7E–02 |
| PA443382 | Anoxia | 230 | 189.06 | 1.10 | 3.1E–04 | 2.7E–02 |
| PA447322 | Therapy-related acute myeloid leukemia (t-ML) | 54 | 44.39 | 1.19 | 3.2E–04 | 2.7E–02 |
| PA443553 | Brain Diseases | 480 | 394.56 | 1.07 | 3.2E–04 | 2.7E–02 |
| PA44406S | Epilepsy | 243 | 199.75 | 1.10 | 3.7E–04 | 3.0E–02 |
| PA165108839 | Psychomotor epilepsy | 53 | 43.57 | 1.19 | 3.8E–04 | 3.06–02 |
| PA443728 | Chromosome Aberrations | 355 | 291.81 | 1.08 | 4.1E–04 | 3.1E–02 |
| PA446309 | Lymphoma, T-Cell | 190 | 156.18 | 1.11 | 4.1E–04 | 3.1E–02 |
| PA444349 | Lymphoproliferative Disorders | 388 | 318.94 | 1.08 | 4.5E–04 | 3.3E–02 |
| PA165108619 | Peripheral neuroepithelioma | 166 | 136.45 | 1.11 | 4.6E–04 | 3.3E–02 |
| OMIM Database | ||||||
| 12S853 | Diabetes mellitus, noninsulin-dependent | 28 | 4.23 | 6.14 | 5.0E–15 | 5.0E–15 |
| 114480 | Breast cancer | 24 | 3.63 | 6.61 | 5.0E–15 | 5.0E–15 |
| 601626 | Leukemia, acute myeloid | 20 | 3.02 | 6.61 | 5.0E–15 | 5.0E–15 |
| 189960 | Tracheoesophageal fistula with or without esophageal atresia | 21 | 3.18 | 5.98 | 3.1E–14 | 1.2E–12 |
| 114500 | Colorectal cancer | 14 | 2.12 | 6.61 | 2.9E–12 | 9.1E–11 |
| 252010 | Mitochondrial complex i deficiency | 18 | 2.72 | 5.51 | 2.2E–10 | 5.1E–09 |
| 211980 | Lung canceralveolar cell carcinoma, included | 16 | 2.42 | 5.79 | 2.5E–10 | 5.1E–09 |
| 256000 | Leigh syndrome | 16 | 2.42 | 5.79 | 2.5E–10 | 5.1E–09 |
| 601665 | Obesityleanness, included | 15 | 2.27 | 5.73 | 1.5E–09 | 2.7E–08 |
| 176807 | Prostate cancer | 12 | 1.81 | 6.06 | 9.0E–09 | 1.4E–07 |
| 609423 | Human immunodeficiency virus type 1, susceptibility | 15 | 2.27 | 5.29 | 3.8E–08 | 5.2E–07 |
| 114550 | Hepatocellular carcinoma | 9 | 1.36 | 6.61 | 3.9E–08 | 5.2E–07 |
| 608446 | Myocardial infarction, susceptibility tomyocardial infarction, susceptibility to, 1, included | 13 | 1.97 | 5.60 | 5.1E–08 | 5.6E–07 |
| 600807 | Asthma, susceptibility to | 11 | 1.66 | 6.01 | 5.6E–08 | 5.6E–07 |
| 104300 | AJiheimer disease | 11 | 1.66 | 6.01 | 5.6E–08 | 5.6E–07 |
| 607948 | Mycobacterium tuberculosis, susceptibility tomycobacterium tuberculosis, protection against | 11 | 1.66 | 6.01 | 5.6E–08 | 5.6E–07 |
| 181500 | Schizophrenia | 14 | 2.12 | 5.20 | 2.0E–07 | 1.9E–06 |
| 180300 | Rheumatoid arthritis | 8 | 1.21 | 6.61 | 2.6E–07 | 2.3E–06 |
| 145500 | Hypertension, essential | 12 | 1.81 | 5.51 | 2.9E–07 | 2.4E–06 |
| 187500 | Tetralogy of fallot | 7 | 1.06 | 6.61 | 1.8E–06 | 1.3E–05 |
| 613065 | Leukemia, acute lymphoblastic | 7 | 1.06 | 6.61 | 1.8E–06 | 1.3E–05 |
| 268000 | Retinitis pigmentosa | 10 | 1.51 | 5.29 | 8.9E–06 | 6.5E–05 |
| 607174 | Meningioma, familial, susceptibility to | 6 | 0.91 | 6.61 | 1.2E–05 | 6.5E–05 |
| 144700 | Renal cell carcinoma, nonpapillary | 6 | 0.91 | 6.61 | 1.2E–05 | 6.5E–05 |
| 143890 | Hypercholesterolemia, familial | 6 | 0.91 | 6.61 | 1.2E–05 | 6.5E–05 |
| 209880 | Central hypoventilation syndrome, congenital | 6 | 0.91 | 6.61 | 1.2E–05 | 6.5E–05 |
| 130650 | Beckwith-wiedemann syndrome | 6 | 0.91 | 6.61 | 1.2E–05 | 6.5E–05 |
| 166710 | Osteoporosis | 6 | 0.91 | 6.61 | 1.2E–05 | 6.5E–05 |
| 171300 | Pheochromocytoma | 8 | 1.21 | 5.79 | 1.2E–05 | 6.5E–05 |
| 613659 | Gastric cancergastric cancer, intestinal, included | 8 | 1.21 | 5.79 | 1.2E–05 | 6.5E–05 |
| 611162 | Malaria, susceptibility tomalaria, resistance to | 17 | 2.57 | 3.89 | 4.1E–05 | 2.1E–04 |
| 217095 | Conotruncal heart malformations | 5 | 0.76 | 6.61 | 7.8E–05 | 3.0E–04 |
| 603932 | Intervertebral disc disease | 5 | 0.76 | 6.61 | 7.8E–05 | 3.0E–04 |
| 608089 | Endometrial cancer | 5 | 0.76 | 6.61 | 7.8E–05 | 3.0E–04 |
| 226650 | Epidermolysis bullosa, junctional, non-herlitz type | 5 | 0.76 | 6.61 | 7.8E–05 | 3.0E–04 |
| 240500 | lmmunodeficiency, common variable, 2 | 5 | 0.76 | 6.61 | 7.8E–05 | 3.0E–04 |
| 609135 | Aplastic anemiaaplastic anemia, susceptibility to | 5 | 0.76 | 6.61 | 7.8E–05 | 3.0E–04 |
| 607785 | Juvenile myelomonocytic leukemia | 5 | 0.76 | 6.61 | 7.8E–05 | 3.0E–04 |
| 188470 | Thyroid cancer, nonmedullary, 2 | 5 | 0.76 | 6.61 | 7.8E–05 | 3.0E–04 |
| 236670 | Muscular dystrophy-dystroglycanopathy (congenital with brain and eyeanomalies), type a, 1 | 5 | 0.76 | 6.61 | 7.8E–05 | 3.0E–04 |
| 603896 | Leukoencephalopathy with vanishing white matter | 5 | 0.76 | 6.61 | 7.8E–05 | 3.0E–04 |
| 176270 | Prader-willi syndrome | 10 | 1.51 | 4.63 | 1.4E–04 | 5.1E–04 |
| 168600 | Parkinson disease, late-onset | 8 | 1.21 | 4.96 | 2.5E–04 | 8.7E–04 |
| 146110 | Hypogonadotropic hypogonadism 7 with or without anosmia | 14 | 2.12 | 3.78 | 3.4E–04 | 1.1E–03 |
| 255310 | Myopathy, congenital, with fiber-type disproportion | 6 | 0.91 | 5.51 | 4.1E–04 | 1.1E–03 |
| 254450 | Myelofibrosismyelofibrosis with myeloid metaplasia | 4 | 0.60 | 6.61 | 5.2E–04 | 1.1E–03 |
| 219700 | Cystic fibrosis | 4 | 0.60 | 6.61 | 5.2E–04 | 1.1E–03 |
| 273300 | Testicular germ cell tumor | 4 | 0.60 | 6.61 | 5.2E–04 | 1.1E–03 |
| 194190 | WoK-Nrschhorn syndrome | 4 | 0.60 | 6.61 | 5.2E–04 | 1.1E–03 |
| 136880 | Fundus albipunctatusretinitis punctata albescens | 4 | 0.60 | 6.61 | 5.2E–04 | 1.1E–03 |
| 209900 | Bardet-biedl syndrome 1 | 7 | 1.06 | 4.72 | 1.3E–03 | 2.7E–03 |
| 415000 | Spermatogenic failure, y–linked, 2 | 8 | 1.21 | 4.13 | 2.9E–03 | 4.5E–03 |
| 606963 | Pulmonary disease, chronic obstructive | 3 | 0.45 | 6.61 | 3.4E–03 | 4.5E–03 |
| 604571 | Bare lymphocyte syndrome, type i | 3 | 0.45 | 6.61 | 3.4E–03 | 4.5E–03 |
| 601410 | Diabetes mellitus, transient neonatal, 1 | 3 | 0.45 | 6.61 | 3.4E–03 | 4.5E–03 |
| 607341 | Focal cortical dysplasia, type ii | 3 | 0.45 | 6.61 | 3.4E–03 | 4.5E–03 |
| 219000 | Fraser syndrome 1 | 3 | 0.45 | 6.61 | 3.4E–03 | 4.5E–03 |
| 231200 | Bernard-soulier syndrome | 3 | 0.45 | 6.61 | 3.4E–03 | 4.5E–03 |
| 264350 | Pseudohypoaldosteronism, type i, autosomal recessive | 3 | 0.45 | 6.61 | 3.4E–03 | 4.5E–03 |
| 259500 | Osteogenic sarcoma | 3 | 0.45 | 6.61 | 3.4E–03 | 4.5E–03 |
| 614519 | Hemorrhage, intracerebral, susceptibility to | 3 | 0.45 | 6.61 | 3.4E–03 | 4.5E–03 |
| 268220 | Rhabdomyosarcoma 2 | 3 | 0.45 | 6.61 | 3.4E–03 | 4.5E–03 |
| 608516 | Major depressive disorder | 3 | 0.45 | 6.61 | 3.4E–03 | 4.5E–03 |
| 231680 | MULTIPLE ACYl–COa DEHYDROGENASE DEFICIENCY | 3 | 0.45 | 6.61 | 3.4E–03 | 4.5E–03 |
| 109400 | Basal cell nevus syndrome | 3 | 0.45 | 6.61 | 3.4E–03 | 4.5E–03 |
| 604229 | Anterior segment dysgenesis 5 | 3 | 0.45 | 6.61 | 3.4E–03 | 4.5E–03 |
| 163200 | Schimmelpenning-feuerstein-mims syndrome | 3 | 0.45 | 6.61 | 3.4E–03 | 4.5E–03 |
| 606864 | Paraganglioma and gastric stromal sarcoma | 3 | 0.45 | 6.61 | 3.4E–03 | 4.5E–03 |
| 613652 | Clq deficiency | 3 | 0.45 | 6.61 | 3.4E–03 | 4.5E–03 |
| 158810 | Bethlem myopathy 1 | 3 | 0.45 | 6.61 | 3.4E–03 | 4.5E–03 |
| 602089 | Hemangioma, capillary infantile | 3 | 0.45 | 6.61 | 3.4E–03 | 4.5E–03 |
| 600791 | Deafness, autosomal recessive 4, with enlarged vestibular aqueduct | 3 | 0.45 | 6.61 | 3.4E–03 | 4.5E–03 |
| 248600 | Maple syrup urine disease | 3 | 0.45 | 6.61 | 3.4E–03 | 4.5E–03 |
| 304400 | Deafness, x-linked 2 | 3 | 0.45 | 6.61 | 3.4E–03 | 4.5E–03 |
| 145900 | Hypertrophic neuropathy of dejerine-sottas | 4 | 0.60 | 4.96 | 1.2E–02 | 1.5E–02 |
| 201300 | Neuropathy, hereditary sensory and autonomic, type iia | 4 | 0.60 | 4.96 | 1.2E–02 | 1.5E–02 |
| 105200 | Amyloidosis, familial visceral | 4 | 0.60 | 4.96 | 1.2E–02 | 1.5E–02 |
| 105400 | Amyotrophic lateral sclerosis 1 | 4 | 0.60 | 4.96 | 1.2E–02 | 1.5E–02 |
| 188890 | Tobacco addiction, susceptibility to | 4 | 0.60 | 4.96 | 1.2E–02 | 1.5E–02 |
| 601634 | Neural lube defects, folate-sensitive | 4 | 0.60 | 4.96 | 1.2E–02 | 1.5E–02 |
| 60307S | Macular degeneration, age-related, 1 | 5 | 0.76 | 3.97 | 2.7E–02 | 3.3E–02 |
These are disease sets overrepresented among gene lists annotated to CpG sites that were associated with pyrethroids at a raw p<0.05. Models controlled for cell count, age, sex, education, and a genetic marker for Hispanic ancestry. Gene lists were derived from WebGestalt, with a minimum gene set size of 3. Gene set overrepresentations for diseases that use the BMIQ normalization are reported in the main findings (Figure 3).