Institute of Genetics and Cancer

DNA modifications associated with poor lung function and COPD

DNA is modified by the environment and genetics to affect the risk of chronic obstructive pulmonary disease. April 2019

Twenty-four COPD cases and thirty non-cases in the Generation Scotland
Twenty-four COPD cases and thirty non-cases in the Generation Scotland: Scottish Family health study cohort were predicted as being at low and high risk of getting COPD using information on sex, age, height and smoking history alone (reduced model), or in addition to DNA modifications associated with respiratory function and chronic obstructive pulmonary disease (COPD; full model). Grey non-cases and red COPD cases denote correctly classified individuals.

University of Edinburgh researchers, led by Kathy Evans and Mairead Bermingham in the Centre for Genomic and Experimental Medicine have shown that DNA modifications seen in the blood can identify people at high risk of developing chronic obstructive pulmonary disease (COPD).

COPD is a life-limiting lung disease. It is the third leading cause of death around the world, according to the World Health Organization, and the 2016 Global Burden of Disease study linked it to 2.9 million deaths that year. An estimated 1.2 million people in the UK are living with diagnosed COPD.

COPD patients develop chronic cough and shortness of breath. In the long term, lung tissue is destroyed. Today's treatments only start after the first obvious signs and can only slow progression.

Smoking is a well-known risk factor, but not the only one. Genes and other environmental factors are thought to play a part, but the mechanism through which they act isn’t clear.

In the largest study to date, the researchers have now pinpointed 28 subtle changes in blood DNA that are linked to lung function and COPD. These changes, called DNA methylation, reflect exposures to factors in the environment such as tobacco smoke, and other irritants that cause inflammation of the lungs, as well as genetic differences between individuals. With further developments, such DNA methylation ‘signatures’ may help early diagnosis and for treatment to be started before irreversible lung damage occurs.

Our study is a promising first step in exploring the potential role of DNA modifications in causing poor lung function and COPD. It also highlights that epigenetic data might be useful in identifying individuals with declining lung function that might benefit from more intensive monitoring and/or therapy.

Dr Mairead BerminghamFirst Author

The research was made possible by participants in Generation Scotland ( and the Lothian Birth Cohort 1936 and was supported by the Wellcome Trust (104036/Z/14/Z).

Identification of novel differentially methylated sites with potential as clinical predictors of impaired respiratory function and COPD’ is published in EBioMedicine. (DOI: 10.1016/j.ebiom.2019.03.072)

Kathy Evans Research Group