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

Department of Health Technology

Research output: Contribution to journal › Journal article › Research › peer-review

67 Downloads (Pure)

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
Number of pages	13
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-022-35088-6
Publication status	Published - 2022

Access to Document

10.1038/s41467-022-35088-6

fulltextFinal published version, 4.05 MB

OpenUrl availability

Full text

Cite this

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{6b7fe67eda1846e585cdd9256da5ceb0,

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 Cheng-Jian Xu",

note = "{\textcopyright} 2022. The Author(s).",

year = "2022",

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, C-ET, 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, C-J 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

PY - 2022

Y1 - 2022

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.

U2 - 10.1038/s41467-022-35088-6

DO - 10.1038/s41467-022-35088-6

M3 - Journal article

C2 - 36456559

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

Abstract

Access to Document

OpenUrl availability

Fingerprint

Cite this