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Table 1 Associations between GDM and methylation of candidate regions assayed by pyrosequencing in validation cohort (RICHS) and verification set (HEBC)

From: Epigenome-wide and transcriptome-wide analyses reveal gestational diabetes is associated with alterations in the human leukocyte antigen complex

A. Locus closest to candidate on microarraya

 

Association with GDM [coef (95 % CI)]

 

Gene in proximity

CpG ID

450K array (beta)

Validation set (%)

Verification set (%)

 

  HLA-DOA

cg08147094

−0.12 (−0.18, −0.06)

−3.24 (−7.93, 1.44)

−13.95* (−20.50, −7.40)

 

  HLA-H/HLA-J

cg23681866

0.11 (0.05, 0.17)

−1.96 (−7.46, 3.54)

6.21 (−0.18, 12.59)

 

  SNRPN/SNURF

cg18506672

−0.09 (−0.13, −0.04)

−0.49 (−2.41, 1.43)

−7.24* (−11.44, −3.04)

 

  CCDC181

cg25464921

0.14 (0.07, 0.21)

−3.28 (−7.90, 1.34)

9.02* (3.53, 14.52)

B. Regional change within pyrosequenced regionb

 

Association with GDM [coef (95 % CI)]

 

Gene in proximity

Size of region (Candidate)

450K array (beta)

Validation set (%)

Verification set (%)

 

  HLA-DOA

2 (CpG 1)

–

−3.01 (−6.17, 0.16)

−9.23* (−13.67, −4.79)

 

  HLA-H/HLA-J

3 (CpG 2)

–

−1.56 (−6.12, 3.01)

4.82 (−0.78, 10.42)

 

  SNRPN/SNURF

2 (CpG 1)

–

−0.44 (−4.70, 3.82)

−4.70 (−10.63, 1.23)

 

  CCDC181

8 (CpG 6)

–

−2.42 (−6.89, 2.04)

9.34* (3.41, 15.27)

  1. aAssociation between GDM and methylation of CpG site assayed by pyrosequencing in closest proximity to the site chosen for validation based on methylation array data. The candidate locus in each region has the strongest association with GDM in our adjusted models. Linear model adjusted for maternal age (years), pre-pregnancy BMI (kg/m2), infant sex, maternal smoking (yes/no), and self-reported ethnicity. Positive values indicate an increase in methylation with GDM
  2. bChange in methylation associated with GDM across pyrosequenced loci modeled using linear mixed models with a random intercept for sample, adjusting for the same covariates. Positive values indicate an increase in methylation with GDM
  3. *p < 0.05