Epigenome-wide meta-analysis of DNA methylation and childhood asthma

Reese, Sarah E.; Xu, Cheng‐Jian; Dekker, Herman T. den; Lee, Mi Kyeong; Sikdar, Sinjini; Ruiz‐Arenas, Carlos; Merid, Simon Kebede; Rezwan, Faisal I.; Page, Christian M.; Ullemar, Vilhelmina; Melton, Phillip E.; Oh, Sam S.; Yang, Ivana V.; Burrows, Kimberley; Söderhäll, Cilla; Jima, Dereje D.; Gao, Lu; Arathimos, Ryan; Küpers, Leanne K.; Wielscher, Matthias; Rzehak, Peter; Lahti, Jari; Laprise, Catherine; Madore, Anne-Marie; Ward, James M.; Bennett, Brian D.; Wang, Tianyuan; Bell, Douglas A.; Vonk, Judith M.; Håberg, Siri E.; Zhao, Shanshan; Karlsson, Robert; Hollams, Elysia M.; Hu, Donglei; Richards, Adam; Bergström, Anna; Sharp, Gemma C; Felix, Janine F.; Bustamante, Mariona; Gruzieva, Olena; Maguire, Rachel; Gilliland, Frank D.; Baïz, Nour; Nøhr, Ellen A.; Corpeleijn, Eva; Sebért, Sylvain; Karmaus, Wilfried; Grote, Veit; Kajantie, Eero; Magnus, Maria C; Örtqvist, Anne K.; Eng, Celeste; Liu, Andrew H.; Kull, Inger; Jaddoe, Vincent W.V.; Sunyer, Jordi; Kere, Juha; Hoyo, Cathrine; Annesi‐Maesano, Isabella; Arshad, Syed Hasan; Koletzko, Berthold; Brunekreef, Bert; Binder, Elisabeth B.; Räikkönen, Katri; Reischl, Eva; Holloway, John W.; Järvelin, Marjo‐Riitta; Snieder, Harold; Kazmi, Nabila; Breton, Carrie V.; Murphy, Susan K.; Pershagen, Göran; Antó, Josep M.; Relton, Caroline L; Schwartz, David A.; Burchard, Esteban G.; Huang, Rae‐Chi; Nystad, Wenche; Almqvist, Catarina; Henderson, A. John; Melén, Erik; Koppelman, Gerard H.; London, Stephanie J.

doi:10.1016/j.jaci.2018.11.043

Cited by 156 publications

(189 citation statements)

References 65 publications

(69 reference statements)

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“…The authors reported that of the FDR significant CpGs, 31 (17%) fell within a significant DMR, and 21 (58%) DMRs contained at least one significant CpG. 33 Upon comparison, no CpGs significant for newborns were significant in childhood. Six CpGs significant for asthma in childhood were at least nominally significant for newborns, two of which had the same direction of effect.…”

Section: Number Of Subjects Methylation Methods Designmentioning

confidence: 99%

“…Reese et al 33 CpGs were identified to be differentially methylated, 173 of which showed decreased methylation. Thirty-six DMRs were identified.…”

Section: Number Of Subjects Methylation Methods Designmentioning

confidence: 99%

“…Two studies did not describe sufficient baseline characteristics. 29,30 Six studies included a validation and replication cohort, [31][32][33][34][35] and one study replicated the reactions and reported a concordance rate. 31 Studies conducted on blood samples employed different approaches in adjusting for differential distribution of cell types: Xu et al 31…”

Section: Quality Assessmentmentioning

confidence: 99%

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Epigenome‐wide association studies in asthma: A systematic review

Edris

Dekker

Melén

et al. 2019

Clin Experimental Allergy

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Objective Asthma is a common chronic respiratory airway disease influenced by environmental factors and possibly their interaction with the human genome causing epigenetic changes. Epigenome‐wide association studies (EWAS) have mainly investigated DNA methylation and its association with disease or traits, exposure factors or gene expression. This systematic review aimed to identify all EWAS assessing differentially methylated sites associated with asthma in humans. Design Structured systematic literature search following PRISMA guidelines, Newcastle‐Ottawa Scale (NOS) for cohort studies was used for bias assessment. Data Sources We searched PubMed and Embase databases from 2005 to 2019. Eligibility Criteria Epigenome‐wide association studies testing association between differential methylation and asthma in humans. Results Overall, we identified 16 EWAS studies complying with our search criteria. Twelve studies were conducted on children, and 10 were conducted on sample sizes <150 subjects. Four hundred and nineteen CpGs were reported in children studies after correction for multiple testing. In the adult studies, thousands of differentially methylated sites were identified. Differential methylation in inflammatory‐related genes correlated with higher levels of gene expressions of inflammatory modulators in asthma. Differentially methylated genes associated with asthma included SMAD3, SERPINC1, PROK1, IL13, RUNX3 and TIGIT. Forty‐one CpGs were replicated at least once in blood samples, and 28 CpGs were replicated in nasal samples. Conclusion Although many differentially methylated CpGs in genes known to be involved in asthma have been identified in EWAS to date, we conclude that further studies of larger sample sizes and analyses of differential methylation between different phenotypes are needed in order to comprehensively evaluate the role of epigenetic factors in the pathophysiology and heterogeneity of asthma, and the potential clinical utility to predict or classify patients with asthma.

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Section: Number Of Subjects Methylation Methods Designmentioning

confidence: 99%

“…Reese et al 33 CpGs were identified to be differentially methylated, 173 of which showed decreased methylation. Thirty-six DMRs were identified.…”

Section: Number Of Subjects Methylation Methods Designmentioning

confidence: 99%

Section: Quality Assessmentmentioning

confidence: 99%

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Epigenome‐wide association studies in asthma: A systematic review

Edris

Dekker

Melén

et al. 2019

Clin Experimental Allergy

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“…The prevalence of immune-mediated diseases is continuously rising. 1,2 In addition to genetic predisposition, socioeconomic circumstances and environmental factors may modulate the development of these diseases. Although the mechanisms leading to abnormal immune responses in autoimmune and allergic diseases may share some common pathways, the detailed pathogenesis of these conditions is still inadequately understood.…”

Section: Coeliac Disease and Hla-conferred Susceptibility To Autoimmumentioning

confidence: 99%

Effects of inhaled corticosteroids on DNA methylation in peripheral blood cells in children with asthma

Kere

Gruzieva

Ullemar

et al. 2019

Allergy

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To the Editor, Asthma is a chronic heterogeneous inflammatory airway disease.Its treatment includes bronchodilators and anti-inflammatory medication such as corticosteroids. Corticosteroids reduce transcription of AP-1 and NF-κB and hence may affect DNA methylation.Epigenetics refers to changes in DNA that can affect transcription, such as methylation of a cytosine nucleotide beside a guanine nucleotide (CpGs).Asthma is associated with differentially methylated CpGs in specific genes. 1,2 In the largest study to date, asthmatic children had significantly lower blood methylation levels at 14 CpGs compared to controls. 3 One previous study found 19 CpGs that were differentially methylated in blood during systemic corticosteroid exposure in patients with COPD. 4 Possible effects of inhaled asthma medication on peripheral blood methylation profiles are currently unknown.Our aim was to study the association between inhaled corticosteroids and DNA methylation in peripheral blood cells in children with asthma. First, we performed an epigenome-wide association study (EWAS) investigating the effects of variable inhaled corticosteroid exposure on DNA methylation in 8-year-olds with diagnosed asthma in the BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology) cohort followed by replication attempts. Second, using a candidate gene approach, we evaluated if identified CpGs from the systemic steroid study 4 and the largest asthma study to date, 3 in total 33 CpGs, were differentially methylated in relation to inhaled asthma treatment.BAMSE is a Swedish prospective birth cohort study. 5 A total of 4089 children born 1994-1996 enrolled and information was collected in repeated questionnaires. Blood samples were taken at the

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“…In other methylation studies on children with asthma, association with several known immune/asthma genes, including IL13 and RUNX3, has been described [29]. Associations between methylation status in newborns and later asthma at school age have also been reported [30].…”

Section: Genetics and Epigeneticsmentioning

confidence: 94%