Second-generation epigenetic clocks show greater promise for disease risk prediction

Epigenetic clocks estimate a person’s ‘biological age’ by measuring patterns of DNA methylation – chemical marks on DNA that can change over time. These clocks were originally designed to predict chronological age, but newer versions – termed second or third generation clocks – can also reflect overall health and changes in health over time. 

In a large-scale study, led by researchers at the Institute of Genetics and Cancer (IGC), 14 commonly used epigenetic clocks were compared across almost 20,000 people from the Generation Scotland study with 10 years of linked clinical records. The team tested how well each clock predicted 174 different diseases and risk of death. 

The study found that several second and third-generation clocks were strong predictors of certain diseases, including lung cancer and diabetes. In 27 diseases, their predictive power was even stronger than their ability to predict overall mortality. For 32 outcomes, adding an epigenetic clock to standard risk factors improved prediction accuracy. The researchers found little evidence that the clocks behaved differently in men versus women or smokers versus non-smokers.

Overall, the study suggests that second and third-generation clocks may be useful for predicting disease risk - especially for respiratory and liver conditions. However, because these clocks incorporate many complex biological signals, they can be hard to interpret in terms of cause and effect. First-generation clocks, though less powerful for disease prediction, may still be better suited for understanding the basic biology of ageing.

Click on the Shiny App built by the research team where you can select clocks/diseases of interest to see how they perform.