The University of Southampton
University of Southampton Institutional Repository

Association of season of birth with DNA methylation and allergic disease

Association of season of birth with DNA methylation and allergic disease
Association of season of birth with DNA methylation and allergic disease
Background: Season of birth influences allergy risk, however the biological mechanisms underlying this observation are unclear. The environment affects DNA methylation, with potentially long-lasting effects on gene expression and disease. This study examined whether DNA methylation could underlie the association between season of birth and allergy.

Methods: In a subset of 18-year-old participants from the Isle of Wight (IoW) birth cohort (n=367), the risks of birth season on allergic outcomes were estimated. Whole blood epigenome-wide DNA methylation was measured, and season-associated CpGs detected using a training-and-testing-based technique. Validation examined the 8-year-old Prevention and Incidence of Asthma and Mite Allergy (PIAMA) cohort. The relationships between DNA methylation, season of birth and allergy were examined. CpGs were analysed in IoW third generation cohort newborns.

Results: Autumn birth increased risk of eczema, relative to spring birth. Methylation at 92 CpGs showed association with season of birth in the epigenome-wide association study. In validation significantly more CpGs had the same directionality than expected by chance, and four were statistically significant. Season-associated methylation was enriched among networks relating to development, the cell cycle, and apoptosis. Twenty CpGs were nominally associated with allergic outcomes. Two CpGs were marginally on the causal pathway to allergy. Season-associated methylation was largely absent in newborns, suggesting it arises postnatally.

Conclusions: This study demonstrates that DNA methylation in adulthood is associated with season of birth, supporting the hypothesis that DNA methylation could mechanistically underlie the effect of season of birth on allergy, though other mechanisms are also likely to be involved.
450K array, dna methlation, eigenetics, epigenome-wide association study, season of birth
0105-4538
1314-1324
Lockett, Gabrielle A.
4d92a28c-f54c-431b-81f6-e82ad9057d7a
Soto-Ramírez, Nelís
3526295b-e2ec-4cf3-bc74-088d10943f45
Ray, Meredith A.
9ad3f4c3-4746-49df-a23a-7549914efa7a
Everson, Todd M.
0639cdab-214c-4fd3-8181-bfca14ad58ef
Xu, Cheng-Jian
1c4d76ae-4c68-4688-8ef6-88ef2529a436
Patil, Veeresh K.
b898b9a7-db31-4c1c-b0f0-4165b3e4d29c
Terry, William
cc83c83e-9021-4767-942a-eb9149b70157
Kaushal, Akhilesh
a7742b05-148f-411e-bd3d-c2c29ecdcfef
Rezwan, Faisal I.
203f8f38-1f5d-485b-ab11-c546b4276338
Ewart, Susan L.
48158071-d7b8-46b5-8aef-26ffb37eec3b
Gehring, Ulrike
3efc6b4a-4367-4686-99ae-c4a278f7e473
Postma, Dirkje S.
23c1567d-a264-48a1-9ab4-01beda374e42
Koppelman, Gerard H.
8d04aab8-5795-4e62-b64a-de7e368c0d1d
Arshad, S. Hasan
917e246d-2e60-472f-8d30-94b01ef28958
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Lockett, Gabrielle A.
4d92a28c-f54c-431b-81f6-e82ad9057d7a
Soto-Ramírez, Nelís
3526295b-e2ec-4cf3-bc74-088d10943f45
Ray, Meredith A.
9ad3f4c3-4746-49df-a23a-7549914efa7a
Everson, Todd M.
0639cdab-214c-4fd3-8181-bfca14ad58ef
Xu, Cheng-Jian
1c4d76ae-4c68-4688-8ef6-88ef2529a436
Patil, Veeresh K.
b898b9a7-db31-4c1c-b0f0-4165b3e4d29c
Terry, William
cc83c83e-9021-4767-942a-eb9149b70157
Kaushal, Akhilesh
a7742b05-148f-411e-bd3d-c2c29ecdcfef
Rezwan, Faisal I.
203f8f38-1f5d-485b-ab11-c546b4276338
Ewart, Susan L.
48158071-d7b8-46b5-8aef-26ffb37eec3b
Gehring, Ulrike
3efc6b4a-4367-4686-99ae-c4a278f7e473
Postma, Dirkje S.
23c1567d-a264-48a1-9ab4-01beda374e42
Koppelman, Gerard H.
8d04aab8-5795-4e62-b64a-de7e368c0d1d
Arshad, S. Hasan
917e246d-2e60-472f-8d30-94b01ef28958
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a

Lockett, Gabrielle A., Soto-Ramírez, Nelís, Ray, Meredith A., Everson, Todd M., Xu, Cheng-Jian, Patil, Veeresh K., Terry, William, Kaushal, Akhilesh, Rezwan, Faisal I., Ewart, Susan L., Gehring, Ulrike, Postma, Dirkje S., Koppelman, Gerard H., Arshad, S. Hasan, Zhang, Hongmei, Karmaus, Wilfried and Holloway, John W. (2016) Association of season of birth with DNA methylation and allergic disease. Allergy, 71 (9), 1314-1324. (doi:10.1111/all.12882). (PMID:26973132)

Record type: Article

Abstract

Background: Season of birth influences allergy risk, however the biological mechanisms underlying this observation are unclear. The environment affects DNA methylation, with potentially long-lasting effects on gene expression and disease. This study examined whether DNA methylation could underlie the association between season of birth and allergy.

Methods: In a subset of 18-year-old participants from the Isle of Wight (IoW) birth cohort (n=367), the risks of birth season on allergic outcomes were estimated. Whole blood epigenome-wide DNA methylation was measured, and season-associated CpGs detected using a training-and-testing-based technique. Validation examined the 8-year-old Prevention and Incidence of Asthma and Mite Allergy (PIAMA) cohort. The relationships between DNA methylation, season of birth and allergy were examined. CpGs were analysed in IoW third generation cohort newborns.

Results: Autumn birth increased risk of eczema, relative to spring birth. Methylation at 92 CpGs showed association with season of birth in the epigenome-wide association study. In validation significantly more CpGs had the same directionality than expected by chance, and four were statistically significant. Season-associated methylation was enriched among networks relating to development, the cell cycle, and apoptosis. Twenty CpGs were nominally associated with allergic outcomes. Two CpGs were marginally on the causal pathway to allergy. Season-associated methylation was largely absent in newborns, suggesting it arises postnatally.

Conclusions: This study demonstrates that DNA methylation in adulthood is associated with season of birth, supporting the hypothesis that DNA methylation could mechanistically underlie the effect of season of birth on allergy, though other mechanisms are also likely to be involved.

Text
all12882.pdf - Accepted Manuscript
Download (324kB)

More information

Accepted/In Press date: 8 March 2016
e-pub ahead of print date: 12 March 2016
Published date: September 2016
Keywords: 450K array, dna methlation, eigenetics, epigenome-wide association study, season of birth
Organisations: Human Development & Health, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 389796
URI: https://eprints.soton.ac.uk/id/eprint/389796
ISSN: 0105-4538
PURE UUID: a245717d-03f1-4a3c-98e5-c88f4e168703
ORCID for Faisal I. Rezwan: ORCID iD orcid.org/0000-0001-9921-222X
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

Catalogue record

Date deposited: 15 Mar 2016 13:46
Last modified: 03 Dec 2019 06:47

Export record

Altmetrics

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×