Research highlights the relationship between DNA methylation and metabolic traits

Researchers at IGC explore the relationship between DNA methylation, metabolic traits and cognitive function using Scottish and Singaporean cohorts.

Understanding the impact that changes in metabolic health have at the molecular level in both health and disease is difficult without reliable molecular markers. 

Identifying molecular markers that are associated with metabolic health measures such as body mass index (BMI) and body fat percentage can improve monitoring of both metabolic health and disease. Identifying these markers can also expand our understanding of the shared and unique biological processes and pathways associated with metabolic health measures. Using a combination of molecular markers as proxies of these traits could also allow a more objective approach to their measurement. One such molecular marker is DNA methylation, a chemical modification that can be dynamically added to different sites across the genome resulting in a change in gene expression. 

University of Edinburgh researchers have examined DNA methylation patterns at more than 700,000 sites across the genomes of more than 17,000 participants from the Generation Scotland cohort. They found DNA methylation at several sites to be associated with six metabolic measures: BMI, body fat percentage, waist-hip ratio, and blood-based measures of glucose, high-density lipoprotein cholesterol, and total cholesterol. 

DNA methylation patterns (also called epigenetic scores or EpiScores) that were predictive of the six metabolic measures in Generation Scotland were considered as proxies for each trait. These EpiScores were also able to explain variance in metabolic health measures in external Scottish (Lothian Birth Cohort 1936) and Singaporean (Health for Life in Singapore) cohorts. 

In addition, these EpiScores were also correlated with cognitive function in the Lothian Birth Cohort 1936, indicating that they may also provide a blood-based signature of brain health. 

This study highlights that EpiScores generated from DNA methylation patterns can act as proxies to estimate metabolic health factors. 

Our study shows that taking different statistical approaches to identifying DNA methylation markers of metabolic traits greatly affects the number of markers identified. Further, the EpiScores of metabolic traits in our study showed promise as an objective way of measuring metabolic health and tracking cognitive function.

Hannah Smith PhD Student, Institute of Genetics and Cancer

It's exciting to see that DNA methylation patterns reflect metabolic health similarly across populations in Scotland and Singapore. An interesting next step would be to test this further in other diverse populations. There are limitations to assessing metabolic health through measures such as BMI, therefore taking the objective approach of using blood-based markers may help us to improve disease risk prediction in the future.

Professor Riccardo Marioni Institute of Genetics and Cancer

These findings were published in The American Journal of Human Genetics in an article entitled ‘DNA methylation-based predictors of metabolic traits in Scottish and Singaporean cohorts’.

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