Methylated CpGs in early life predict lung function in subsequent periods
Shadia Khan Sunny (Memphis, United States of America), Shadia Khan Sunny, Akhilesh Kaushal, Hongmei Zhang, S. Hasan Arshad, John W. Holloway, Wilfried Karmaus
Source: International Congress 2016 – Important factors, besides smoking, that relate to lung function and decline in lung function
Disease area: Airway diseases, Paediatric lung diseases
Abstract Background: Lung function is the key clinical marker for asthma; it may be influenced by the epigenetic mechanisms e.g. DNA methylation (DNA-M). However, no study has shown the role of DNA-M to predict lung function.Objectives: To explore whether the specific methylated cytosine-phosphate-guanine sites (CpGs) across the epigenome at early life can predict the lung functions in later periods.Methods: The Isle of Wight birth cohort was established in 1989. The current analysis focuses on girls. DNA-M levels were measured from peripheral blood spots and samples collected from neonates (n =30) and at age 10 (n =34), using the Illumina Infinium HumanMethylation450 BeadChip. Spirometric tests were conducted at ages 10 and 18. A total of 274,709 CpGs were included in two prediction periods (PPs): neonatal DNA-M to lung function at age 10 (PP1) and DNA-M at age 10 to lung function at 18 (PP2) using a training and testing screening method. Screened CpGs were corroborated in linear regression adjusted for confounders and the false discovery rate. Then we compared whether significant CpGs identified in one PP were also significantly associated with lung function in other PP.Results: In PP1, 3 CpGs and 20 in PP2 were identified with statistically significant similar effects (P value range 5.2E-06 to 0.0496) in both periods. Among these loci, a number of genes are known to be involved in lung disease, for instance,TIE1, RARB, EBF3, IRX4 , and TBCD were found to be related with lung function; PRDM16, PTPRG, PRDM1, TIAM2, MEIS1 and NME2 were linked to lung cancer.Conclusions: Screening for CpGs in early life may help to identify children at higher risk of reduced lung function and serve as candidate loci for future studies.
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Shadia Khan Sunny (Memphis, United States of America), Shadia Khan Sunny, Akhilesh Kaushal, Hongmei Zhang, S. Hasan Arshad, John W. Holloway, Wilfried Karmaus. Methylated CpGs in early life predict lung function in subsequent periods. Eur Respir J 2016; 48: Suppl. 60, 5003
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