What is the chance you will get this disease?
Research supported in part by the EU-funded INTERVENE project has led to a new framework for estimating the risk that someone will develop a disease during their lifetime, based on polygenic scores (PGSs). The framework, which takes into account age, sex and country-specific differences in its risk estimates for high-burden diseases, could help health policymakers create better screening tools for the early prevention of common diseases. PGSs combine the total number of genetic variants that an individual has in order to assess their risk of developing a particular disease. These scores help to predict genetic risk for complex diseases across the course of a person’s life. However, to produce estimates that could aid clinical and public health decision-making, the varying effects of common risk factors such as age and sex also need to be taken into account. The research team therefore developed their novel framework to estimate country-, age- and sex-specific estimates of cumulative incidence stratified by PGSs for 18 high-burden diseases. To demonstrate their method, the researchers combined disease incidences from the Global Burden of Disease with PGS associations in about 1.2 million individuals from seven studies in four countries. Their results were published in the journal ‘Nature Communications’. According to the findings, PGSs have a significant sex-specific effect for asthma, hip osteoarthritis, gout, coronary heart disease and type 2 diabetes (T2D), with all but T2D exhibiting a greater effect in men than women. PGSs were also found to have a larger effect on younger individuals for 13 out of the 18 diseases studied, with the effects decreasing linearly with age.
A useful screening tool
The results indicate how PGS-based stratification can affect risk-based screening practices. For T2D, men and women in the top 1 % of polygenic risk reached the risk threshold at 24.8 and 22.3 years of age, respectively. However, individuals in the bottom 1 % did not reach the risk threshold by age 80. For breast cancer, the study reports that relative to individuals in the bottom 20 % of polygenic risk, the top 5 % reach the risk threshold 16.3 years earlier. This suggests that PGS could be highly useful as a screening tool for many diseases. Study co-senior author Prof. Samuli Ripatti of INTERVENE (International consortium for integrative genomics prediction) project coordinator University of Helsinki, Finland, comments: “Our study highlights the power of combining 1.2 million biobanked samples across Europe. This allowed us for the first time to show that in many diseases the effects of polygenic risk scores are much higher in young individuals compared to older participants and some effects are also different for males and females. These observations may have implications when implementing the risk scores to clinical practice.” For more information, please see: INTERVENE project website
Keywords
INTERVENE, polygenic risk, polygenic score, disease, screening, high-burden disease