An epigenetic study of more than 18,000 people has found links between DNA methylation and diseases including breast cancer and type 2 diabetes.
Writing in the journal PLoS Medicine, researchers at the University of Edinburgh described the results of an analysis of DNA methylation at around 750,000 cytosine-phosphate-guanine dinucleotide (CpG) sites in whole-blood samples. DNA methylation at CpG sites is an epigenetic modification to DNA that alters the activity of genes. The reversible process is affected by factors such as diet, stress, and smoking.
Earlier epigenome-wide association studies (EWAS) identified methylation changes as potential markers of disease, revealing, for example, that changes to regulators of glucose and cholesterol metabolism are associated with an increased risk of type 2 diabetes. However, many earlier EWAS were relatively small, studying samples from fewer than 1,000 people, and differences between the studies limited the utility of meta-analyses of pooled data from different sources.
The PLoS Medicine paper was designed to address those limitations. Analyzing samples taken from 18,413 volunteers in the family-structured, population-based cohort study Generation Scotland, the researchers looked for associations between CpG methylation and 19 disease states. The disease information came from questionnaires that participants completed at the start of the study and from Scottish health records.
Through the analysis, the researchers identified 69 associations between CpGs and the prevalence of four conditions: breast cancer, chronic kidney disease, ischemic heart disease, and type 2 diabetes. The majority (58) of the associations had not previously been described in the literature. The analysis also revealed 64 CpGs associated with the incidence of chronic obstructive pulmonary disease (COPD) and type 2 diabetes. Again, most (56) of the CpGs were newly described.
“These associations were independent of common lifestyle risk factors,” the researchers wrote. “However, we also observe a vast number of additional associations whereby CpGs index or track associations between lifestyle factors and common disease states, further highlighting the appropriateness of [DNA methylation] as a biomarker of lifestyle behavior.”
The findings suggest that blood DNA methylation could serve as a peripheral marker of common disease states including breast cancer, cardiopulmonary disease, and type 2 diabetes. DNA methylation in blood samples may fail to reflect the patterns seen in tissues, such as changes in the nervous systems of people with Alzheimer’s disease, but blood samples are simple to obtain and may still be useful in some areas.