Epigenome-Wide Association Study of Chronic Obstructive Pulmonary Disease and Lung Function in Koreans

Abstract

Aim: To identify differentially methylated probes (DMPs) and regions (DMRs) in relation to chronic obstructive pulmonary disease (COPD) and lung function traits. Methods: We performed an epigenome-wide association study of COPD and spirometric parameters, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC, in blood DNA using the Infinium HumanMethylation450 (n = 100, a Korean COPD cohort). Results: We found one significant DMP (cg03559389, DIP2C) and 104 significant DMRs after multiple-testing correction. Of these, 34 DMRs mapped to genes differential expressed with respect to the same trait. Five of the genes were associated with more than two traits: CTU2, USP36, ZNF516, KLK10 and CPT1B. Conclusion: We identified novel differential methylation loci related to COPD and lung function in blood DNA in Koreans and confirmed previous findings in non-Asians. Epigenetic modification could contribute to the etiology of these phenotypes.

Keywords::

• chronic obstructive pulmonary disease
• DNA methylation
• epigenome-wide association study
• gene expression
• lung function

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at:www.tandfonline.com/doi/full/10.2217/epi-2017-0002

Acknowledgements

The authors appreciate all of the study participants for their contribution to this research. The authors thank F Day, T Wang and S Reese of NIEHS and J Jin of Westat, Inc. for expert computational assistance.

Financial & competing interest disclosure

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2013R1A1A1057961, 2017R1A2B4003790), the Ministry of Education (2013R1A6A3A04059017) and grants from the Environmental Health Center funded by the Ministry of Environment, Republic of Korea. Supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (ZO1 ES043012). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The Institute Review Board of the Kangwon National University Hospital approved analyses of the data (Institutional Review Board of Kangwon National University Hospital 2012-06-007-001 and KNUH-2016–05-003-001). Informed written consent was obtained from all participants. The study adhered to the tenets of the Helsinki Declaration of 1975, as revised in 2008.

Additional information

Funding

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2013R1A1A1057961, 2017R1A2B4003790), the Ministry of Education (2013R1A6A3A04059017) and grants from the Environmental Health Center funded by the Ministry of Environment, Republic of Korea. Supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (ZO1 ES043012). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.