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DNA methylation and allergic sensitizations, a genome-scale longitudinal study during adolescence

DNA methylation and allergic sensitizations, a genome-scale longitudinal study during adolescence
DNA methylation and allergic sensitizations, a genome-scale longitudinal study during adolescence
Background: the presence of allergic sensitization has a major influence on the development and course of common childhood conditions such as asthma and rhinitis. The etiology of allergic sensitization is poorly understood and its underlying biological mechanisms are not well established. Several studies showed that DNA methylation (DNAm) at some CpGs is associated with allergic sensitization. However, no studies have focused on the critical adolescence period.

Methods: we assessed the association of pre- and post-adolescence genome-wide DNAm with allergic sensitization against indoor, outdoor and food allergens, using linear mixed models. We hypothesized that DNAm is associated with sensitization in general, and with poly-sensitization status, and these associations are ageand gender-specific. We tested these hypotheses in the IoW cohort (n=376) and examined the findings in the BAMSE cohort (n=267).

Results: via linear mixed models, we identified 35 CpGs in IoW associated with allergic sensitization (at false discovery rate of 0.05), of which 33 were available in BAMSE and replicated with respect to the direction of associations with allergic sensitization. At the 35 CpGs except for cg19210306 on C13orf27, a reduction in methylation among atopic subjects was observed, most notably for cg21220721 and cg11699125 (ACOT7). DNAm at cg10159529 was strongly correlated with expression of IL5RA in peripheral blood (p-value=6.76×10-20). Three CpGs (cg14121142, cg23842695, and cg26496795) were identified in IoW with age-specific association between DNAm and allergic sensitization.

Conclusion: in adolescence, the status of allergic sensitization was associated with DNAm differentiation and at some CpGs the association is likely to be age-specific.
0105-4538
1166-1175
Zhang, Hongmei
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Kaushal, Akhilesh
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Merid, Simon Kebede
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Mélen, Erik
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Pershagen, Göran
03caa17f-1cf0-4cd9-b432-34885ce8368e
Rezwan, Faisal I
203f8f38-1f5d-485b-ab11-c546b4276338
Han, L.
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Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Arshad, Syed
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Karmaus, Wilfried
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Holloway, John
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Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Kaushal, Akhilesh
a7742b05-148f-411e-bd3d-c2c29ecdcfef
Merid, Simon Kebede
97470f65-a3fd-4aaf-8637-e0dea6f1114e
Mélen, Erik
fb91c6d2-75f4-48c1-87d7-3105cd900612
Pershagen, Göran
03caa17f-1cf0-4cd9-b432-34885ce8368e
Rezwan, Faisal I
203f8f38-1f5d-485b-ab11-c546b4276338
Han, L.
d6ab1481-8d55-43f4-b7ed-ba63d6daa2c1
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Arshad, Syed
917e246d-2e60-472f-8d30-94b01ef28958
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Holloway, John
4bbd77e6-c095-445d-a36b-a50a72f6fe1a

Zhang, Hongmei, Kaushal, Akhilesh, Merid, Simon Kebede, Mélen, Erik, Pershagen, Göran, Rezwan, Faisal I, Han, L., Ewart, Susan, Arshad, Syed, Karmaus, Wilfried and Holloway, John (2019) DNA methylation and allergic sensitizations, a genome-scale longitudinal study during adolescence. Allergy, 74 (6), 1166-1175. (doi:10.1111/all.13746).

Record type: Article

Abstract

Background: the presence of allergic sensitization has a major influence on the development and course of common childhood conditions such as asthma and rhinitis. The etiology of allergic sensitization is poorly understood and its underlying biological mechanisms are not well established. Several studies showed that DNA methylation (DNAm) at some CpGs is associated with allergic sensitization. However, no studies have focused on the critical adolescence period.

Methods: we assessed the association of pre- and post-adolescence genome-wide DNAm with allergic sensitization against indoor, outdoor and food allergens, using linear mixed models. We hypothesized that DNAm is associated with sensitization in general, and with poly-sensitization status, and these associations are ageand gender-specific. We tested these hypotheses in the IoW cohort (n=376) and examined the findings in the BAMSE cohort (n=267).

Results: via linear mixed models, we identified 35 CpGs in IoW associated with allergic sensitization (at false discovery rate of 0.05), of which 33 were available in BAMSE and replicated with respect to the direction of associations with allergic sensitization. At the 35 CpGs except for cg19210306 on C13orf27, a reduction in methylation among atopic subjects was observed, most notably for cg21220721 and cg11699125 (ACOT7). DNAm at cg10159529 was strongly correlated with expression of IL5RA in peripheral blood (p-value=6.76×10-20). Three CpGs (cg14121142, cg23842695, and cg26496795) were identified in IoW with age-specific association between DNAm and allergic sensitization.

Conclusion: in adolescence, the status of allergic sensitization was associated with DNAm differentiation and at some CpGs the association is likely to be age-specific.

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Allergic Sensitization DNA Allergy Journal - Accepted Manuscript
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More information

Accepted/In Press date: 8 January 2019
e-pub ahead of print date: 14 February 2019
Published date: 1 June 2019

Identifiers

Local EPrints ID: 427633
URI: http://eprints.soton.ac.uk/id/eprint/427633
ISSN: 0105-4538
PURE UUID: 7159b5e9-14ce-43ca-99b9-c6630d357963
ORCID for Faisal I Rezwan: ORCID iD orcid.org/0000-0001-9921-222X
ORCID for John Holloway: ORCID iD orcid.org/0000-0001-9998-0464

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Date deposited: 24 Jan 2019 17:30
Last modified: 18 Feb 2021 16:49

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