Epigenome-Wide DNA Methylation Study of IgE Concentration in Relation to Self-Reported Allergies

Abstract

Aim: Epigenetic mechanisms are critical for normal immune development and epigenetic alterations might therefore be possible contributors to immune diseases. To investigate if DNA methylation in whole blood is associated with total and allergen-specific IgE levels. Methods: We performed an epigenome-wide association study to investigate the association between DNA methylation and IgE level, allergen-specific IgE and self-reported immune diseases and allergies in 728 individuals. Results: We identified and replicated 15 CpG sites associated with IgE, mapping to biologically relevant genes, including ACOT7, ILR5A, KCNH2, PRG2 and EPX. A total of 331 loci were associated with allergen-specific IgE, but none of these CpG sites were associated with self-reported allergies and immune diseases. Conclusion: This study shows that IgE levels are associated with DNA methylation levels at numerous CpG sites, which might provide new leads for investigating the links between IgE and allergic inflammation.

Keywords::

• allergy
• DNA methylation
• Fx5
• IgE
• immune diseases
• Phadiatop

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/Full/10.2217/epi-2016-0158

Acknowledgements

We are grateful to all the participants from the community for their interest and willingness to contribute to this study. The computations were performed on resources provided by SNIC through Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) under projects b2011203, p2012153 and b2013110.

Financial & competing interests disclosure

The DNA methylation study in NSPHS has been funded by Swedish Medical Research Council (project number 2011-2354) and the Göran Gustafssons Foundation. The NSPHS study was funded by the Swedish Medical Research Council (project number K2007-66X-20270-01-3) and the Foundation for Strategic Research (SSF). NSPHS as part of EUROSPAN (European Special Populations Research Network) was also supported by European Commission FP6 STRP grant number 01947 (LSHG-CT-2006-01947). Illumina genotyping and DNA methylation analyses was performed by the SNP & SEQ Technology Platform in Uppsala, which is supported by Uppsala University, Uppsala University Hospital, Science for Life Laboratory (SciLifeLab) – Uppsala and the Swedish Research Council (Contracts 80576801 and 70374401). This work has also been supported by the Swedish Society for Medical Research (SSMF), the Kjell och Märta Beijers Foundation, The Marcus Borgström Foundation, the Åke Wiberg foundation and the Vleugels Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

The DNA methylation study in NSPHS has been funded by Swedish Medical Research Council (project number 2011-2354) and the Göran Gustafssons Foundation. The NSPHS study was funded by the Swedish Medical Research Council (project number K2007-66X-20270-01-3) and the Foundation for Strategic Research (SSF). NSPHS as part of EUROSPAN (European Special Populations Research Network) was also supported by European Commission FP6 STRP grant number 01947 (LSHG-CT-2006-01947). Illumina genotyping and DNA methylation analyses was performed by the SNP & SEQ Technology Platform in Uppsala, which is supported by Uppsala University, Uppsala University Hospital, Science for Life Laboratory (SciLifeLab) – Uppsala and the Swedish Research Council (Contracts 80576801 and 70374401). This work has also been supported by the Swedish Society for Medical Research (SSMF), the Kjell och Märta Beijers Foundation, The Marcus Borgström Foundation, the Åke Wiberg foundation and the Vleugels Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.