Methylation risk scores for childhood aeroallergen sensitization:
Results from the LISA birth cohort
Abstract
Background It has been hypothesized that epigenomic modifications such
as genomic methylation changes are an intermediate step linking
environmental exposures with allergic disease development. Associations
between individual DNA methylation CpG sites and allergic diseases have
been reported, but they have not been assessed regarding their joint
predictive capability. Methods Data were obtained from 240 children of
the German LISA cohort. Blood-based DNA methylation was measured at six
and ten years. Aeroallergen sensitization, at least RAST class 1, was
measured in blood at six, ten and 15 years. We calculated six
methylation risk scores (MRS) for allergy-related phenotypes based on
available publications and assessed their performance both
cross-sectionally and prospectively. Dose-response associations between
aeroallergen sensitization and MRS, their correlation and mapping of
common hits were evaluated. Results All six atopy-related MRS were
highly correlated (r>0.86) and seven CpGs were included in
more than one MRS. Cross-sectionally, we observed an 80% increased risk
for aeroallergen sensitization at six years with an increased risk score
by one standard deviation (best MRS: relative risk = 1.81, 95%
confidence interval = [1.43; 2.27]). Significant associations were
also seen at ten years and in prospective models, though the effect of
the latter was attenuated when only including participants not
sensitized at baseline. A clear dose-response relationship with RAST
classes of aeroallergen sensitization could be established
cross-sectionally, but not prospectively. Conclusion We found good
classification and prediction capabilities of calculated allergy-related
MRS, particularly cross-sectionally for the allergy prevalence,
underlining the relevance of altered gene-regulation in allergic
diseases.