Shared DNA methylation signatures in childhood allergy: The MeDALL study
BACKGROUND: Differential DNA methylation associated with allergy might provide novel insights into the shared or unique etiology of asthma, rhinitis, and eczema. OBJECTIVE: We sought to identify DNA methylationprofilesassociated with childhood allergy. METHODS: Within the European Mechanisms of the...
| Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | article |
| Publication Date: | 2021 |
| Country: | España |
| Institution: | Universidad del País Vasco |
| Repository: | Addi. Archivo Digital para la Docencia y la Investigación |
| OAI Identifier: | oai:addi.ehu.eus:10810/50775 |
| Online Access: | http://hdl.handle.net/10810/50775 |
| Access Level: | Open access |
| Keyword: | DNA methylation epigenetics IgE allergy children |
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Shared DNA methylation signatures in childhood allergy: The MeDALL studyXu, Cheng-JianGruzieva, OlenaQi, CancanEsplugues, AnaGehring, UlrikeBergström, AnnaMason, DanChatzi, LedaPorta, DanielaLodrup Carlsen, Karin C.Baïz, NourMadore, Anne-MarieAlenius, HarriVan Rijkom, BiancaJankipersadsing, Soesma A.Van der Vlies, PieterKull, IngerVan Hage, MarianneBustamante, MarionaLertxundi Manterola, AitanaTorrent, MatiasSantore, GillianFantini, Maria PiaHovland, VegardPesce, GiancarloBIOS ConsortiumFyhrquist, NannaLaatikainen, TiinaNawijn, Martijn C.Li, YangWijmenga, CiscaNetea, Mihai G.Bousquet, JeanAntó, Josep M.Laprise, CatherineHaahtela, TariAnnesi-Maesano, IsabellaCarlsen, Kai-HåkonGori, DavideKogevinas, ManolisWright, JohnSöderhäll, CillaVonk, Judith M.Sunyer, JordiMelén, ErikKoppelman, Gerard H.DNA methylationepigeneticsIgEallergychildrenBACKGROUND: Differential DNA methylation associated with allergy might provide novel insights into the shared or unique etiology of asthma, rhinitis, and eczema. OBJECTIVE: We sought to identify DNA methylationprofilesassociated with childhood allergy. METHODS: Within the European Mechanisms of the Development of Allergy (MeDALL) consortium, we performed an epigenome-wide association study of whole blood DNA methylation by using a cross-sectional design. Allergy was defined as having symptoms from at least 1 allergic disease (asthma, rhinitis, or eczema) and positive serum-specific IgE to common aeroallergens. The discovery study included 219 case patients and 417 controls at age 4 years and 228 case patients and 593 controls at age 8 years from 3 birth cohorts, with replication analyses in 325 case patients and 1111 controls. We performed additional analyses on 21 replicated sites in 785 case patients and 2124 controls by allergic symptoms only from 8 cohorts, 3 of which were not previously included in analyses. RESULTS: We identified 80 differentially methylated CpG sites that showed a 1% to 3% methylation difference in the discovery phase, of which 21 (including 5 novel CpG sites) passed genome-wide significance after meta-analysis. All 21 CpG sites were also significantly differentially methylated with allergic symptoms and shared between asthma, rhinitis, and eczema. The 21 CpG sites mapped to relevant genes, including ACOT7, LMAN3, and CLDN23. All 21 CpG sties were differently methylated in asthma in isolated eosinophils, and 10 were replicated in respiratory epithelium. CONCLUSION: Reduced whole blood DNA methylation at 21 CpG sites was significantly associated with childhood allergy. The findings provide novel insights into the shared molecular mechanisms underlying asthma, rhinitis, and eczema.Elsevier202120212021info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/50775reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoIngléshttps://www.sciencedirect.com/science/article/pii/S0091674920317668?via%3Dihubinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/3.0/es/2020 The Authors. Published by Elsevier Inc. on behalf of the American Academy ofAllergy, Asthma & Immunology. This is an open access article under the CC BY li-cense (http://creativecommons.org/licenses/by/4.0/)Atribución 3.0 Españaoai:addi.ehu.eus:10810/507752026-06-18T09:23:17Z |
| dc.title.none.fl_str_mv |
Shared DNA methylation signatures in childhood allergy: The MeDALL study |
| title |
Shared DNA methylation signatures in childhood allergy: The MeDALL study |
| spellingShingle |
Shared DNA methylation signatures in childhood allergy: The MeDALL study Xu, Cheng-Jian DNA methylation epigenetics IgE allergy children |
| title_short |
Shared DNA methylation signatures in childhood allergy: The MeDALL study |
| title_full |
Shared DNA methylation signatures in childhood allergy: The MeDALL study |
| title_fullStr |
Shared DNA methylation signatures in childhood allergy: The MeDALL study |
| title_full_unstemmed |
Shared DNA methylation signatures in childhood allergy: The MeDALL study |
| title_sort |
Shared DNA methylation signatures in childhood allergy: The MeDALL study |
| dc.creator.none.fl_str_mv |
Xu, Cheng-Jian Gruzieva, Olena Qi, Cancan Esplugues, Ana Gehring, Ulrike Bergström, Anna Mason, Dan Chatzi, Leda Porta, Daniela Lodrup Carlsen, Karin C. Baïz, Nour Madore, Anne-Marie Alenius, Harri Van Rijkom, Bianca Jankipersadsing, Soesma A. Van der Vlies, Pieter Kull, Inger Van Hage, Marianne Bustamante, Mariona Lertxundi Manterola, Aitana Torrent, Matias Santore, Gillian Fantini, Maria Pia Hovland, Vegard Pesce, Giancarlo BIOS Consortium Fyhrquist, Nanna Laatikainen, Tiina Nawijn, Martijn C. Li, Yang Wijmenga, Cisca Netea, Mihai G. Bousquet, Jean Antó, Josep M. Laprise, Catherine Haahtela, Tari Annesi-Maesano, Isabella Carlsen, Kai-Håkon Gori, Davide Kogevinas, Manolis Wright, John Söderhäll, Cilla Vonk, Judith M. Sunyer, Jordi Melén, Erik Koppelman, Gerard H. |
| author |
Xu, Cheng-Jian |
| author_facet |
Xu, Cheng-Jian Gruzieva, Olena Qi, Cancan Esplugues, Ana Gehring, Ulrike Bergström, Anna Mason, Dan Chatzi, Leda Porta, Daniela Lodrup Carlsen, Karin C. Baïz, Nour Madore, Anne-Marie Alenius, Harri Van Rijkom, Bianca Jankipersadsing, Soesma A. Van der Vlies, Pieter Kull, Inger Van Hage, Marianne Bustamante, Mariona Lertxundi Manterola, Aitana Torrent, Matias Santore, Gillian Fantini, Maria Pia Hovland, Vegard Pesce, Giancarlo BIOS Consortium Fyhrquist, Nanna Laatikainen, Tiina Nawijn, Martijn C. Li, Yang Wijmenga, Cisca Netea, Mihai G. Bousquet, Jean Antó, Josep M. Laprise, Catherine Haahtela, Tari Annesi-Maesano, Isabella Carlsen, Kai-Håkon Gori, Davide Kogevinas, Manolis Wright, John Söderhäll, Cilla Vonk, Judith M. Sunyer, Jordi Melén, Erik Koppelman, Gerard H. |
| author_role |
author |
| author2 |
Gruzieva, Olena Qi, Cancan Esplugues, Ana Gehring, Ulrike Bergström, Anna Mason, Dan Chatzi, Leda Porta, Daniela Lodrup Carlsen, Karin C. Baïz, Nour Madore, Anne-Marie Alenius, Harri Van Rijkom, Bianca Jankipersadsing, Soesma A. Van der Vlies, Pieter Kull, Inger Van Hage, Marianne Bustamante, Mariona Lertxundi Manterola, Aitana Torrent, Matias Santore, Gillian Fantini, Maria Pia Hovland, Vegard Pesce, Giancarlo BIOS Consortium Fyhrquist, Nanna Laatikainen, Tiina Nawijn, Martijn C. Li, Yang Wijmenga, Cisca Netea, Mihai G. Bousquet, Jean Antó, Josep M. Laprise, Catherine Haahtela, Tari Annesi-Maesano, Isabella Carlsen, Kai-Håkon Gori, Davide Kogevinas, Manolis Wright, John Söderhäll, Cilla Vonk, Judith M. Sunyer, Jordi Melén, Erik Koppelman, Gerard H. |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
DNA methylation epigenetics IgE allergy children |
| topic |
DNA methylation epigenetics IgE allergy children |
| description |
BACKGROUND: Differential DNA methylation associated with allergy might provide novel insights into the shared or unique etiology of asthma, rhinitis, and eczema. OBJECTIVE: We sought to identify DNA methylationprofilesassociated with childhood allergy. METHODS: Within the European Mechanisms of the Development of Allergy (MeDALL) consortium, we performed an epigenome-wide association study of whole blood DNA methylation by using a cross-sectional design. Allergy was defined as having symptoms from at least 1 allergic disease (asthma, rhinitis, or eczema) and positive serum-specific IgE to common aeroallergens. The discovery study included 219 case patients and 417 controls at age 4 years and 228 case patients and 593 controls at age 8 years from 3 birth cohorts, with replication analyses in 325 case patients and 1111 controls. We performed additional analyses on 21 replicated sites in 785 case patients and 2124 controls by allergic symptoms only from 8 cohorts, 3 of which were not previously included in analyses. RESULTS: We identified 80 differentially methylated CpG sites that showed a 1% to 3% methylation difference in the discovery phase, of which 21 (including 5 novel CpG sites) passed genome-wide significance after meta-analysis. All 21 CpG sites were also significantly differentially methylated with allergic symptoms and shared between asthma, rhinitis, and eczema. The 21 CpG sites mapped to relevant genes, including ACOT7, LMAN3, and CLDN23. All 21 CpG sties were differently methylated in asthma in isolated eosinophils, and 10 were replicated in respiratory epithelium. CONCLUSION: Reduced whole blood DNA methylation at 21 CpG sites was significantly associated with childhood allergy. The findings provide novel insights into the shared molecular mechanisms underlying asthma, rhinitis, and eczema. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021 2021 2021 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10810/50775 |
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http://hdl.handle.net/10810/50775 |
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Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
https://www.sciencedirect.com/science/article/pii/S0091674920317668?via%3Dihub |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/3.0/es/ Atribución 3.0 España |
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openAccess |
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http://creativecommons.org/licenses/by/3.0/es/ Atribución 3.0 España |
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application/pdf |
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Elsevier |
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Elsevier |
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