Table 2.
Overview of epigenetic analyses and results
| Methylation data | Research question | Statistical modela | Results | Significance threshold |
|---|---|---|---|---|
| EPIC array | Are CpG-sites on the EPIC array differentially methylated with regard to BET exposure? | summary (lm (beta ~ child’s sex + gestational age + PC1 + PC2 + PC3 + PC4 + pregnant person’s age + smoking during pregnancy + cell type PC1 + cell type PC2 + BET)) | cg22363520 (chr6, bp 35,558,488) is differentially methylated with BET | epigenome-wide, p < 9 × 10–08, based on Mansell et al. [31] |
| TBS FKBP5 | Are CpG-sites within FKBP5 differentially methylated with regard to BET exposure? | summary (lm (beta ~ child’s sex + gestational age + PC1 + PC2 + PC3 + PC4 + pregnant person’s age + smoking during pregnancy + cell type PC1 + cell type PC2 + plate + BET)) | PCR_2_29 (intron7, bp 35,558,488) is differentially methylated with BET | FDR 5% over all investigated CpG-sites in FKBP5 |
| TBS FKBP5 | Are CpG-sites within FKBP5 differentially methylated with regard to the functional variant rs1360780? | summary (lm (beta ~ child’s sex + gestational age + PC1 + PC2 + PC3 + PC4 + pregnant person’s age + smoking during pregnancy + cell type PC1 + cell type PC2 + plate + rs1360780)) |
PCR_2_262 (intron 7, bp 35,558,721) PCR_12_47 (intron 1, bp 35,630,996) PCR_12_62 (intron 1, bp 35,631,011) PCR_12_211 (intron 1, bp 35,631,160) PCR_17_63 (proximal enhancer, bp 35,695,192) PCR_20_191 (proximal enhancer, bp 35,696,886) are differentially methylated with rs1360780 |
FDR 5% over all investigated CpG-sites in FKBP5 |
| TBS FKBP5 | Are additive effects of the functional variant rs1360780 and BET on DNAm in FKBP5 present? | summary (lm (beta ~ child’s sex + gestational age + PC1 + PC2 + PC3 + PC4 + pregnant person’s age + smoking during pregnancy + cell type PC1 + cell type PC2 + plate + rs1360780 + BET)) | additive effects of rs1360780 and BET on DNAm of PCR_2_29 (intron7, bp 35,558,488) | FDR 5% over all investigated CpG-sites in FKBP5 |
| TBS FKBP5 | Are interactive effects of the functional variant rs1360780 and BET on DNAm in FKBP5 present? | summary (lm (beta ~ child’s sex + gestational age + PC1 + PC2 + PC3 + PC4 + pregnant person’s age + smoking during pregnancy + cell type PC1 + cell type PC2 + plate + rs1360780 + BET + rs1360780 x BET)) | no interactive effects after correction for multiple testing | FDR 5% over all investigated CpG-sites in FKBP5 |
PC1–PC4 refer to the first four MDS components, correcting for ethnicity. Cell type PC1, cell type PC2 refer to the first two components from a PCA on the cell types (see Methods). Plate refers to TBS plate (see Methods). bp is the base-pair position (hg19).
aStatistical model refers to linear model as set up in R