Does pregnancy change the effect of methQTL on DNA methylation and alter the risk of eczema?

RATIONALE: Single nucleotide polymorphisms (SNPs) may act as methylation quantitative trait loci (methQTLs) and influence the variation of DNA-methylation. The effect of methQTLs on methylation may change with exposures such as pregnancy. We hypothesized that pregnancy changes the effect of methQTLs on the methylation of CpGs (cytosine-phosphate-guanine dinucleotides) leading to the development of eczema during pregnancy.

METHODS: Peripheral blood samples were obtained at age 18 years and during early pregnancy from the F1-generation of Ilse of Wight birth cohort, UK (n=249 and n=109, respectively). Methylation profiles were generated using the Illumina Infinium HumanMethylaton450 and EPIC Beadchips. Two layers of screening were implemented to: (1) identify SNPs associated with eczema in women repeatedly measured at age 1, 2, 4, 10, 18 years and pregnancy and (2) focus on CpGs affected by these eczema-associated methQTLs. Then linear mixed models with repeated measurements were applied to assess the interaction of methQTLs and pregnancy on methylation, and the joint effect of methylation and pregnancy on eczema, controlling for methQTLs.

RESULTS: During pregnancy, 38 women had eczema. The methylation of cg11798521 (STAT6 gene) is significantly associated with eczema regardless of pregnancy, controlling for its methQTL (rs1059513). In addition, the methylation of CpG (cg03848267) changes with pregnancy and has a statistically stronger effect (p-value=0.0097) on eczema than at age 18, adjusting for the methQTL (rs1059513).

CONCLUSIONS: The effect of a methQTL on methylation can change over time and/or with an exposure such as pregnancy. Pregnancy seems to increase the risk of the development of eczema through a variation in methylation.