Table 3.
Methylation marks that partially mediate the association between pesticide exposure and leptin and body fat accumulation in PON1-192 R-allele carriers
| Outcome | IlmnID | Nearest gene symbol | Gene name | Direction of methylation in exposed R carriers | Diseases | Significance of causal mediation effect (P value) |
|---|---|---|---|---|---|---|
| Leptin | cg03366858 | LRP8 | Low density lipoprotein receptor-related protein 8, apolipoprotein e receptor | Hyper | Myocardial infarction (0.22)|nerve degeneration (0.21)|Myocardial infarction, susceptibility to, 1 (finding) (0.2) | 0.02 |
| Leptin | cg18202502 | LRP8 | Low density lipoprotein receptor-related protein 8, apolipoprotein e receptor | Hyper | Myocardial infarction (0.22) | nerve degeneration (0.21)|myocardial infarction, susceptibility to, 1 (finding) (0.2) | 0.024 |
| Delta BMI Z score | cg00810945 | UQCRC2 | Ubiquinol-cytochrome c reductase core protein II | Hypo | Mitochondrial complex iii deficiency, nuclear type 5 (0.41) | obesity (0.21) | 0.138 |
| Delta BMI Z score | cg06337557 | MTNR1B | Melatonin receptor 1B | Hypo | Diabetes mellitus, Type 2 (0.26)|polycystic ovary syndrome (0.21) | child development disorders, pervasive (0.21)|acute pancreatitis (0.1) | 0.032 |
| Delta BMI Z score | cg14152613 | FABP4 | Fatty acid-binding protein 4, adipocyte | Hyper | Carcinoma (0.21)|mammary neoplasms, experimental (0.21) | mammary neoplasms, animal (0.21)|insulin resistance (0.1)|erectile dysfunction (0.1)|diabetes mellitus, experimental (0.1) | 0.068 |
| Delta BMI Z score | cg15134033 | GRIN2A | Glutamate receptor, ionotropic, N-methyl D-aspartate 2A | Hypo | Epilepsy (0.21)|colorectal neoplasms (0.21)|epilepsy, rolandic (0.21)|melanoma (0.21)|landau-kleffner syndrome (0.21)|autistic disorder (0.21)|morphine dependence (0.21)|language development disorders (0.21)|epilepsy, focal, with speech disorder and with or without mental retardation (0.21)|speech disorders (0.21)|substance withdrawal syndrome (0.21)|rolandic epilepsy, mental retardation, and speech dyspraxia, autosomal dominant (0.2)|reperfusion injury (0.1)|hypoxia-ischemia, brain (0.1)|sepsis (0.1)|fetal growth retardation (0.1)|central nervous system viral diseases (0.1)|placental insufficiency (0.1) | 0.144 |
| Delta BMI Z score | cg18202502 | LRP8 | Low density lipoprotein receptor-related protein 8, apolipoprotein e receptor | Hyper | Myocardial infarction (0.22)|nerve degeneration (0.21)|myocardial infarction, susceptibility to, 1 (finding) (0.2) | 0.026 |
| Bodyfat | cg00810945 | UQCRC2 | Ubiquinol-cytochrome c reductase core protein II | Hypo | Mitochondrial complex iii deficiency, nuclear type 5 (0.41)|obesity (0.21) | 0.174 |
| Bodyfat | cg03366858 | LRP8 | Low density lipoprotein receptor-related protein 8, apolipoprotein e receptor | Hyper | Myocardial infarction (0.22)|nerve degeneration (0.21)|myocardial infarction, susceptibility to, 1 (finding) (0.2) | <0.001 |
| Bodyfat | cg18202502 | LRP8 | Low density lipoprotein receptor-related protein 8, apolipoprotein e receptor | Hyper | Myocardial infarction (0.22)|nerve degeneration (0.21)|myocardial infarction, susceptibility to, 1 (finding) (0.2) | <0.001 |
Only the subset of genes for which associations with metabolic disease have been reported is listed. DisGeNET Score—indicating reliability of the gene disease associations—is included between brackets