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Table 4 Number of significant associations between PFAS with 5-mC and/or 5-hmC (n = 70)

From: Mediation effects of DNA methylation and hydroxymethylation on birth outcomes after prenatal per- and polyfluoroalkyl substances (PFAS) exposure in the Michigan mother–infant Pairs cohort

 

5-mC/5-hmC Interaction

(q < 0.2)

5-mC Only

(q < 0.05)

5-hmC Only

(q < 0.05)

PFHxS

105

80

101

PFOS

1516

24

1388

PFOA

637

1

0

PFNA

2281

879

1684

PFDA

8054

3527

7432

PFUnDA

3103

361

2507

MeFOSAA

272

164

264

  1. Counts of the number of CpG sites with statistically significant associations between each PFAS and methylation (n = 70 for all analyses). 5-mC/5-hmC-interaction models were used to select the sites to stratify by each type of methylation. The following models were fit, where bolded term indicates the estimate of interest generating the counts above:
  2. \(\begin{aligned} 5 - {\text{mC}}\;{\text{or}}\;5 - {\text{hmC}}\;{\text{proportion}}\;{\text{at}}\;{\text{528}},{\text{389}}\;{\text{Sites}} & = \beta _{0} + \beta _{1} {\text{PFAS}} + \beta _{2} {\text{Parity}} + \beta _{3} {\text{Smoking}} + \beta _{4} {\text{Race}} \\ & \quad + \beta _{5} {\text{sex}} + \beta _{6} {\text{CD}}4{\text{T}} + \beta _{7} {\text{CD}}8{\text{T}} + \beta _{8} {\text{GranCell}} \\ & \quad + \beta _{9} n{\text{RBC}} + \beta _{{10}} {\text{PC}}1 + \beta _{{11}} {\text{PC}}2 + \beta _{{12}} {\text{Type}} \\ & \quad + \varvec{\beta }_{{{\mathbf{13}}}} {\mathbf{Type*PFAS}} + [1|ID] \\ \end{aligned}\)
  3. \(5 - {\text{mC}}\;{\text{or}}\;5 - hmC\;{\text{Methylation}}\;{\text{at}}\;{\text{Sites}}\;{\text{with}}\;{\text{Type}} - {\text{Interaction}} \, = \, \beta _{0} + \varvec{\beta }_{{\mathbf{1}}} {\mathbf{PFAS}} + \beta _{2} {\text{Parity}} + \beta _{3} {\text{Smoking}} + \beta _{4} {\text{Race}} + \beta _{5} {\text{CD4T}} + \beta _{6} {\text{CD}}8{\text{T}} + \beta _{7} {\text{GranCell}} + \beta _{8} n{\text{RBC}} + \beta _{9} {\text{PC}}1 + \beta _{{10}} {\text{PC}}\)
  4. CD4T: CD4 T lymphocytes; CD8T: CD8 T lymphocytes; GranCell: granulated cells; MeFOSAA: 2-(N-methyl-perfluorooctane sulfonamido) acetic acid; nRBC: nucleated red blood cells; PC: principal component representing batch effects; PFAS: per-/polyfluoroalkyl substances; PFHxS: perfluorohexanesulphonic acid; PFDA: perfluorodecanoic acid; PFNA: perfluorononanoic acid; PFOA: perfluorooctanoic acid; PFOS: perfluorooctanesulfonic acid; PFUnDA: perfluoroundecanoic acid