DNA methylation in childhood asthma : an epigenome-wide meta-analysis

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Xu , C-J , Soderhall , C , Bustamante , M , Baiz , N , Gruzieva , O , Gehring , U , Mason , D , Chatzi , L , Basterrechea , M , Llop , S , Torrent , M , Forastiere , F , Fantini , M P , Carlsen , K C L , Haahtela , T , Morin , A , Kerkhof , M , Merid , S K , van Rijkom , B , Jankipersadsing , S A , Bonder , M J , Ballereau , S , Vermeulen , C J , Aguirre-Gamboa , R , de Jongste , J C , Smit , H A , Kumar , A , Pershagen , G , Guerra , S , Garcia-Aymerich , J , Greco , D , Reinius , L , McEachan , R R C , Azad , R , Hovland , V , Mowinckel , P , Alenius , H , Fyhrquist , N , Lemonnier , N , Pellet , J , Auffray , C , van der Vlies , P , van Diemen , C C , Li , Y , Wijmenga , C , Netea , M G , Moffatt , M F , Cookson , W O C M , Anto , J M & Kere , J 2018 , ' DNA methylation in childhood asthma : an epigenome-wide meta-analysis ' , The Lancet respiratory medicine , vol. 6 , no. 5 , pp. 379-388 . https://doi.org/10.1016/S2213-2600(18)30052-3

Title: DNA methylation in childhood asthma : an epigenome-wide meta-analysis
Author: Xu, Cheng-Jian; Soderhall, Cilla; Bustamante, Mariona; Baiz, Nour; Gruzieva, Olena; Gehring, Ulrike; Mason, Dan; Chatzi, Leda; Basterrechea, Mikel; Llop, Sabrina; Torrent, Maties; Forastiere, Francesco; Fantini, Maria Pia; Carlsen, Karin C. Lodrup; Haahtela, Tari; Morin, Andreanne; Kerkhof, Marjan; Merid, Simon Kebede; van Rijkom, Bianca; Jankipersadsing, Soesma A.; Bonder, Marc Jan; Ballereau, Stephane; Vermeulen, Cornelis J.; Aguirre-Gamboa, Raul; de Jongste, Johan C.; Smit, Henriette A.; Kumar, Ashish; Pershagen, Goran; Guerra, Stefano; Garcia-Aymerich, Judith; Greco, Dario; Reinius, Lovisa; McEachan, Rosemary R. C.; Azad, Raf; Hovland, Vegard; Mowinckel, Petter; Alenius, Harri; Fyhrquist, Nanna; Lemonnier, Nathanael; Pellet, Johann; Auffray, Charles; van der Vlies, Pieter; van Diemen, Cleo C.; Li, Yang; Wijmenga, Cisca; Netea, Mihai G.; Moffatt, Miriam F.; Cookson, William O. C. M.; Anto, Josep M.; Kere, Juha
Contributor: University of Helsinki, Department of Dermatology, Allergology and Venereology
University of Helsinki, Medicum
University of Helsinki, Medicum
Date: 2018-05
Language: eng
Number of pages: 10
Belongs to series: The Lancet respiratory medicine
ISSN: 2213-2600
URI: http://hdl.handle.net/10138/301557
Abstract: Background DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma. Methods We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blood in 207 children with asthma and 610 controls at age 4-5 years, and 185 children with asthma and 546 controls at age 8 years using a cross-sectional case-control design. After identification of differentially methylated CpG sites in the discovery analysis, we did a validation study in children (4-16 years; 247 cases and 2949 controls) from six additional European cohorts and meta-analysed the results. We next investigated whether replicated CpG sites in cord blood predict later asthma in 1316 children. We subsequently investigated cell-type-specific methylation of the identified CpG sites in eosinophils and respiratory epithelial cells and their related gene-expression signatures. We studied cell-type specificity of the asthma association of the replicated CpG sites in 455 respiratory epithelial cell samples, collected by nasal brushing of 16-year-old children as well as in DNA isolated from blood eosinophils (16 with asthma, eight controls [age 2-56 years]) and compared this with whole-blood DNA samples of 74 individuals with asthma and 93 controls (age 1-79 years). Whole-blood transcriptional profiles associated with replicated CpG sites were annotated using RNA-seq data of subsets of peripheral blood mononuclear cells sorted by fluorescence-activated cell sorting. Findings 27 methylated CpG sites were identified in the discovery analysis. 14 of these CpG sites were replicated and passed genome-wide significance (p Interpretation Reduced whole-blood DNA methylation at 14 CpG sites acquired after birth was strongly associated with childhood asthma. These CpG sites and their associated transcriptional profiles indicate activation of eosinophils and cytotoxic T cells in childhood asthma. Our findings merit further investigations of the role of epigenetics in a clinical context.
Subject: GENOMEWIDE ASSOCIATION
PHENOTYPES
CHILDREN
COHORT
IGE
POPULATION
COLLECTION
EXPOSURE
RHINITIS
IMMUNITY
3121 General medicine, internal medicine and other clinical medicine
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