Institute of Genetics and Cancer

Over 100 associations between blood DNA methylation sites and common disease states identified

Researchers from the Institute of Genetics and Cancer have established a comprehensive map of epigenetic associations with common human diseases

DNA helix manifesting from cigarette smoke

In a study recently published in PLOS Medicine, Dr Robert Hillary, Professor Riccardo Marioni and colleagues explored the association between DNA methylation and 19 major disease outcomes using the Generation Scotland resource. Methylation is a chemical modification, which when occurring on DNA molecules can affect whether genes are turned on or off. These modifications record the body’s response to different environmental and lifestyle stressors over a life-course, rendering these epigenetic signals as potential biomarkers of human health and disease.

The study identified over 100 associations between DNA methylation sites and the existence or development of five common conditions -  (breast cancer, chronic kidney disease, ischemic heart disease and type 2 diabetes and chronic obstructive pulmonary disease).

This work was possible due to the data collected by the Generation Scotland study. Over 18,000 volunteers in Generation Scotland provided blood samples and completed health questionnaires between 2006 and 2011. Methylation patterns in blood were examined at over 750,000 specific sites across the genome. Participants reported whether they had ever been diagnosed with one of several common diseases, such as heart disease, cancer and type 2 diabetes.

First, the authors examined whether those who reported an existing diagnosis had different methylation patterns than those who did not. 69 associations were identified between specific DNA methylation sites and a pre-existing diagnosis of four conditions: breast cancer, chronic kidney disease, ischemic heart disease, and type 2 diabetes. Of these, 58 were newly discovered.

Next, new cases of 19 different disease states were monitored using linkage to medical records over a 14 year follow up period. The researchers examined whether methylation patterns at the beginning of the study were different in those who went on to develop a given condition versus those who did not. The study identified 64 DNA methylation sites that associated with the future incidence of chronic obstructive pulmonary disease and type 2 diabetes, of which 56 were newly described.  

The diseases considered in the study represented the leading causes of morbidity and death globally. The authors accounted for factors such as age, sex, and lifestyle traits (such as smoking and alcohol consumption) in an attempt to ensure the associations between methylation and disease weren’t due to other risk factors.

Furthermore, they searched scientific literature databases to identify existing studies on DNA methylation and all diseases under investigation. This allowed the researchers to assess whether studies that examined the same condition report similar results to one another.  

This study highlights the potential of using DNA methylation as a biomarker for human health and disease. However, there is a need for replication across studies in order to identify the most reliable associations.  We recommend standardised workflows across different studies and collaborative efforts between population studies to in order to help achieve this goal.

Dr Robert HillaryCentre for Genomic and Experimental Medicine and Usher Institute