Nasal DNA methylation at three CpG sites predicts childhood allergic disease

Merlijn van Breugel; Cancan Qi; Zhongli Xu; Casper Emil T. Pedersen; Ilya Petoukhov; Judith M. Vonk; Ulrike Gehring; Marijn Berg; Marnix Bügel; Orestes A. Carpaij; Erick Forno; Andréanne Morin; Anders U. Eliasen; Yale Jiang; Maarten van den Berge; Martijn C. Nawijn; Yang Li; Wei Chen; Louis J. Bont; Klaus Bønnelykke; Juan C. Celedón; Gerard H. Koppelman; Cheng Jian Xu

doi:10.1038/s41467-022-35088-6

Nasal DNA methylation at three CpG sites predicts childhood allergic disease

Merlijn van Breugel, Cancan Qi, Zhongli Xu, Casper Emil T. Pedersen, Ilya Petoukhov, Judith M. Vonk, Ulrike Gehring, Marijn Berg, Marnix Bügel, Orestes A. Carpaij, Erick Forno, Andréanne Morin, Anders U. Eliasen, Yale Jiang, Maarten van den Berge, Martijn C. Nawijn, Yang Li, Wei Chen, Louis J. Bont, Klaus BønnelykkeJuan C. Celedón, Gerard H. Koppelman, Cheng Jian Xu^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Childhood allergic diseases, including asthma, rhinitis and eczema, are prevalent conditions that share strong genetic and environmental components. Diagnosis relies on clinical history and measurements of allergen-specific IgE. We hypothesize that a multi-omics model could accurately diagnose childhood allergic disease. We show that nasal DNA methylation has the strongest predictive power to diagnose childhood allergy, surpassing blood DNA methylation, genetic risk scores, and environmental factors. DNA methylation at only three nasal CpG sites classifies allergic disease in Dutch children aged 16 years well, with an area under the curve (AUC) of 0.86. This is replicated in Puerto Rican children aged 9–20 years (AUC 0.82). DNA methylation at these CpGs additionally detects allergic multimorbidity and symptomatic IgE sensitization. Using nasal single-cell RNA-sequencing data, these three CpGs associate with influx of T cells and macrophages that contribute to allergic inflammation. Our study suggests the potential of methylation-based allergy diagnosis.

Original language	English
Article number	7415
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-35088-6
Publication status	Published - Dec 2022

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van Breugel, M., Qi, C., Xu, Z., Pedersen, C. E. T., Petoukhov, I., Vonk, J. M., Gehring, U., Berg, M., Bügel, M., Carpaij, O. A., Forno, E., Morin, A., Eliasen, A. U., Jiang, Y., van den Berge, M., Nawijn, M. C., Li, Y., Chen, W., Bont, L. J., ... Xu, C. J. (2022). Nasal DNA methylation at three CpG sites predicts childhood allergic disease. Nature Communications, 13(1), Article 7415. https://doi.org/10.1038/s41467-022-35088-6

@article{26c7deeb467946519316d47464ebdbdf,

title = "Nasal DNA methylation at three CpG sites predicts childhood allergic disease",

abstract = "Childhood allergic diseases, including asthma, rhinitis and eczema, are prevalent conditions that share strong genetic and environmental components. Diagnosis relies on clinical history and measurements of allergen-specific IgE. We hypothesize that a multi-omics model could accurately diagnose childhood allergic disease. We show that nasal DNA methylation has the strongest predictive power to diagnose childhood allergy, surpassing blood DNA methylation, genetic risk scores, and environmental factors. DNA methylation at only three nasal CpG sites classifies allergic disease in Dutch children aged 16 years well, with an area under the curve (AUC) of 0.86. This is replicated in Puerto Rican children aged 9–20 years (AUC 0.82). DNA methylation at these CpGs additionally detects allergic multimorbidity and symptomatic IgE sensitization. Using nasal single-cell RNA-sequencing data, these three CpGs associate with influx of T cells and macrophages that contribute to allergic inflammation. Our study suggests the potential of methylation-based allergy diagnosis.",

author = "{van Breugel}, Merlijn and Cancan Qi and Zhongli Xu and Pedersen, {Casper Emil T.} and Ilya Petoukhov and Vonk, {Judith M.} and Ulrike Gehring and Marijn Berg and Marnix B{\"u}gel and Carpaij, {Orestes A.} and Erick Forno and Andr{\'e}anne Morin and Eliasen, {Anders U.} and Yale Jiang and {van den Berge}, Maarten and Nawijn, {Martijn C.} and Yang Li and Wei Chen and Bont, {Louis J.} and Klaus B{\o}nnelykke and Celed{\'o}n, {Juan C.} and Koppelman, {Gerard H.} and Xu, {Cheng Jian}",

note = "Funding Information: The PIAMA study was supported by The Netherlands Organization for Health Research and Development; The Netherlands Organization for Scientific Research; Lung Foundation of the Netherlands (with methylation studies supported by AF 4.1.14.001); The Netherlands Ministry of Spatial Planning, Housing, and the Environment; The Netherlands Ministry of Health, Welfare, and Sport; and the Ubbo Emmius Foundation. Yang Li was supported by an ERC Starting Grant (948207) and the Radboud University Medical Centre Hypatia Grant (2018) for Scientific Research. Cancan Qi was supported by a grant from the China Scholarship Council. Cheng-Jian Xu was supported by the Helmholtz Initiative and Networking Fund (1800167). Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41467-022-35088-6",

language = "English",

volume = "13",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

van Breugel, M, Qi, C, Xu, Z, Pedersen, CET, Petoukhov, I, Vonk, JM, Gehring, U, Berg, M, Bügel, M, Carpaij, OA, Forno, E, Morin, A, Eliasen, AU, Jiang, Y, van den Berge, M, Nawijn, MC, Li, Y, Chen, W, Bont, LJ, Bønnelykke, K, Celedón, JC, Koppelman, GH & Xu, CJ 2022, 'Nasal DNA methylation at three CpG sites predicts childhood allergic disease', Nature Communications, vol. 13, no. 1, 7415. https://doi.org/10.1038/s41467-022-35088-6

TY - JOUR

T1 - Nasal DNA methylation at three CpG sites predicts childhood allergic disease

AU - van Breugel, Merlijn

AU - Qi, Cancan

AU - Xu, Zhongli

AU - Pedersen, Casper Emil T.

AU - Petoukhov, Ilya

AU - Vonk, Judith M.

AU - Gehring, Ulrike

AU - Berg, Marijn

AU - Bügel, Marnix

AU - Carpaij, Orestes A.

AU - Forno, Erick

AU - Morin, Andréanne

AU - Eliasen, Anders U.

AU - Jiang, Yale

AU - van den Berge, Maarten

AU - Nawijn, Martijn C.

AU - Li, Yang

AU - Chen, Wei

AU - Bont, Louis J.

AU - Bønnelykke, Klaus

AU - Celedón, Juan C.

AU - Koppelman, Gerard H.

AU - Xu, Cheng Jian

N1 - Funding Information: The PIAMA study was supported by The Netherlands Organization for Health Research and Development; The Netherlands Organization for Scientific Research; Lung Foundation of the Netherlands (with methylation studies supported by AF 4.1.14.001); The Netherlands Ministry of Spatial Planning, Housing, and the Environment; The Netherlands Ministry of Health, Welfare, and Sport; and the Ubbo Emmius Foundation. Yang Li was supported by an ERC Starting Grant (948207) and the Radboud University Medical Centre Hypatia Grant (2018) for Scientific Research. Cancan Qi was supported by a grant from the China Scholarship Council. Cheng-Jian Xu was supported by the Helmholtz Initiative and Networking Fund (1800167). Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - Childhood allergic diseases, including asthma, rhinitis and eczema, are prevalent conditions that share strong genetic and environmental components. Diagnosis relies on clinical history and measurements of allergen-specific IgE. We hypothesize that a multi-omics model could accurately diagnose childhood allergic disease. We show that nasal DNA methylation has the strongest predictive power to diagnose childhood allergy, surpassing blood DNA methylation, genetic risk scores, and environmental factors. DNA methylation at only three nasal CpG sites classifies allergic disease in Dutch children aged 16 years well, with an area under the curve (AUC) of 0.86. This is replicated in Puerto Rican children aged 9–20 years (AUC 0.82). DNA methylation at these CpGs additionally detects allergic multimorbidity and symptomatic IgE sensitization. Using nasal single-cell RNA-sequencing data, these three CpGs associate with influx of T cells and macrophages that contribute to allergic inflammation. Our study suggests the potential of methylation-based allergy diagnosis.

AB - Childhood allergic diseases, including asthma, rhinitis and eczema, are prevalent conditions that share strong genetic and environmental components. Diagnosis relies on clinical history and measurements of allergen-specific IgE. We hypothesize that a multi-omics model could accurately diagnose childhood allergic disease. We show that nasal DNA methylation has the strongest predictive power to diagnose childhood allergy, surpassing blood DNA methylation, genetic risk scores, and environmental factors. DNA methylation at only three nasal CpG sites classifies allergic disease in Dutch children aged 16 years well, with an area under the curve (AUC) of 0.86. This is replicated in Puerto Rican children aged 9–20 years (AUC 0.82). DNA methylation at these CpGs additionally detects allergic multimorbidity and symptomatic IgE sensitization. Using nasal single-cell RNA-sequencing data, these three CpGs associate with influx of T cells and macrophages that contribute to allergic inflammation. Our study suggests the potential of methylation-based allergy diagnosis.

UR - http://www.scopus.com/inward/record.url?scp=85143186071&partnerID=8YFLogxK

U2 - 10.1038/s41467-022-35088-6

DO - 10.1038/s41467-022-35088-6

M3 - Article

C2 - 36456559

AN - SCOPUS:85143186071

SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 7415

ER -

Nasal DNA methylation at three CpG sites predicts childhood allergic disease

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