Table 4 Differentially methylated positions that mediate genetic risk in PA.

From: Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children

DMP†

DMP annotation

DMP–rs7192 associations§

DMP–rs9275596 associations§

DMP–PA associations

P for the CIT test††

 

Position

Nearest gene

Location‡

β ‖

P

β ‖

P

β #

P**

rs7192

rs9275596

cg17039645

32294503

C6orf10

Gene body

0.04

4.4 × 10−14

0.03

7.1 × 10−9

0.05

5.4 × 10−7

0.162

0.155

cg18111114

32498493

HLA-DRB5

TSS1500

0.10

5.5 × 10−25

0.09

3.2 × 10−22

0.10

1.6 × 10−5

0.098

0.037

cg15982117

32552106

HLA-DRB1

Gene body

−0.09

8.9 × 10−10

−0.09

3.1 × 10−10

−0.15

3.8 × 10−7

0.002*

0.002*

cg18024368

32632848

HLA-DQB1

Gene body

−0.04

2.7 × 10−10

−0.05

3.1 × 10−13

−0.06

2.4 × 10−6

0.002*

0.003*

  1. CIT, causal inference tests; DMP, differentially methylated position; GWAS, genome-wide association study; PA, peanut allergy; SNP, single-nucleotide polymorphism; TSS, transcription start site.
  2. *P<0.05 after Bonferroni correction for four tested DMPs and two SNPs (cutoff: P<0.006 for 8 tests).
  3. †Represented by Infinium HumanMethylation450 BeadChip probe name. For each gene, only the top DMP that was genome-wide significantly associated with both SNPs (P<5 × 10−8) and that had the strongest association with risk of PA is shown.
  4. ‡Location of the methylation CpG site, in relation to the nearest gene.
  5. §Linear regression models were applied to test SNP–DMP associations in a subset of 218 children of European ancestry with available GWAS data and DNA methylation data, with adjustment of age, gender and the estimated cell composition.
  6. ‖Adjusted methylation difference with an increase of one copy of the risk allele (T allele for rs7192; or C allele for rs9275596).
  7. Linear regression models were applied to test the DMP-PA associations in 73 PA cases and 67 controls of European ancestry, with adjustment of age, gender and the estimated cell composition.
  8. #Adjusted methylation difference between 73 PA cases and 67 controls of European ancestry.
  9. **P<0.00069 (=0.05/72) represents the significance level after Bonferroni correction.
  10. ††Causal inference tests (CIT) were performed for the 4 DMPs in 73 peanut allergic cases and 67 controls of European ancestry using the modified version for binary outcomes.
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