Table 2.
High-dimensional mediation analysis for the association between PM10 (exposure), DNAm (mediator) and neurodevelopment (outcome) using DACT for CpG sites identified via formal causal mediation analysis with a significant indirect effect and total effect
| Chr | Pos | Closest gene | Cognition | Languageb | General Adaptiveb | ||||
|---|---|---|---|---|---|---|---|---|---|
| Raw p-value | FDR | Raw p-value | FDR | Raw p-value | FDR | ||||
| cg13690126 | 1 | 26,502,524 | CNKSR1 | 1.29E−4 | 3.30E−3 | 3.50E−4 | 5.60E−3 | – | – |
| cg07070893 | 1 | 44,412,074 | RP11-7O11.3 | 4.20E−4 | 7.50E−3 | –a | – | – | – |
| cg23560546 | 2 | 159,652,019 | DAPL1 | 7.20E−4 | 0.011 | – | – | – | – |
| cg15007548 | 2 | 159,950,276 | TANC1 | 3.70E−3 | 0.039 | – | – | – | – |
| cg16975959 | 2 | 223,184,510 | AC010980.2 | 1.80E−3 | 0.022 | – | – | – | – |
| cg00694520 | 2 | 223,916,687 | KCNE4 | 3.30E−3 | 0.044 | – | – | – | – |
| cg08967927 | 5 | 30,346,164 | RP11-136H13.2 | 4.29E−05 | 1.40E−3 | – | – | – | – |
| cg22572779 | 6 | 10,434,761 | RP1-290I10.7 | 4.5E−4 | 7.70E−3 | – | – | – | – |
| cg15074838 | 6 | 32,406,521 | HLA-DRA | 2.60E−4 | 5.50E−3 | – | – | – | – |
| cg26668632 | 6 | 137,540,814 | IFNGR1 | 2.90E−4 | 5.50E−3 | – | – | – | – |
| cg01550799 | 7 | 114,561,804 | MDFIC | 1.80E−3 | 0.022 | – | – | – | – |
| cg25405984 | 10 | 31,074,039 | ZNF438 | 2.90E−3 | 0.031 | – | – | – | – |
| cg25544551 | 12 | 104,531,891 | NFYB | 1.51E−05 | 6.40E−4 | – | – | – | – |
| cg19187486 | 15 | 74,833,838 | ARID3B | 3.30E−13 | 5.87E−11 | – | – | – | – |
| cg05796992 | 15 | 101,547,339 | LRRK1 | 4.39E−05 | 1.40E−3 | – | – | – | – |
| cg06233301 | 16 | 1,500,359 | CLCN7 | 2.30E−3 | 0.027 | – | – | – | – |
| cg01085137 | 16 | 48,278,085 | ABCC11 | 1.10E−3 | 0.015 | – | – | – | – |
| cg23989635 | 16 | 68,771,203 | CDH1 | 1.10E−3 | 0.015 | – | – | – | – |
| cg26756782 | 16 | 89,922,218 | SPIRE2 | 5.90E−05 | 1.60E−3 | – | – | – | – |
| cg26894552 | 17 | 5,323,715 | RPAIN | 2.60E−3 | 0.029 | – | – | – | – |
| cg13465852 | 17 | 27,942,115 | CORO6 | 2.36E−10 | 2.10E−08 | – | – | – | – |
| cg10159032 | 17 | 30,347,989 | LRRC37B | 2.20E−4 | 5.30E−3 | – | – | – | – |
| cg14714923 | 17 | 43,238,186 | HEXIM2 | 2.34E−07 | 1.66E−05 | – | – | – | – |
| cg15000966 | 17 | 73,128,123 | NT5C | 1.62E−05 | 6.4E−4 | – | – | – | – |
| cg14243899 | 17 | 74,580,397 | ST6GALNAC2 | 9.00E−4 | 0.013 | – | – | – | – |
| cg23054321 | 19 | 2,289,682 | LINGO3 | 3.36E−07 | 1.99E−05 | – | – | 6.97E−09 | 6.76E−07 |
| cg05023582 | 19 | 50,093,541 | PRRG2 | 2.42E−11 | 2.87E−09 | – | – | – | – |
| cg03234186 | 19 | 58,220,657 | ZNF551 | 8.94E−16 | 3.18E−13 | 3.05E−26 | 1.26E−23 | – | – |
| cg00660655 | 21 | 46,368,151 | FAM207A | 7.20E−4 | 0.011 | – | – | – | – |
This table includes raw and corrected p-values from the DACT method for CpG sites identified across domains restricted to those for which we found with nominally significant indirect effects and total effects (domain-dependent) via causal mediation analysis following high-dimensional mediation analysis (BH FDR < = 0.05)
aMissingness in this table is resultant of our DACT filtering process which is described in more detail in the methods section
35 CpG sites were considered for multiple testing correction in the cognition domain, 45 in the language domain,
39 in the general adaptive behavior domain, and 13 in the motor function domain
bNo CpG sites with both a significant indirect effect and significant total effect were identified in the language, motor, or general adaptive behavior domains. Two significant CpG sites identified in the cognitive domain overlap with two in the language domain and one in the general adaptive domain and therefore, information for two CpG sites identified with DACT are depicted for the language domain and one for the general adaptive domain alongside the cognition domain