Sporadic, late-onset, and multistage diseases

Abstract

Abstract Multistage disease processes are often characterized by a linear relationship between the log of incidence rates and the log of age. Examples include sequences of somatic mutations, that can cause cancer, and have recently been linked with a range of non-malignant diseases. Using a Weibull distribution to model diseases that occur through an ordered sequence of stages, and another model where stages can occur in any order, we characterized the age-related onset of disease in UK Biobank data. Despite their different underlying assumptions, both models accurately described the incidence of over 450 diseases, demonstrating that multistage disease processes cannot be inferred from this data alone. The parametric models provided unique insights into age-related disease, that conventional studies of relative risks cannot. The rate at which disease risk increases with age was used to distinguish between “sporadic” diseases, with an initially low and slowly increasing risk, and “late-onset” diseases whose negligible risk when young rapidly increases with age. “Relative aging rates” were introduced to quantify how risk factors modify age-related risk, finding the effective age-at-risk of sporadic diseases is strongly modified by common risk factors. Relative aging rates are ideal for risk-stratification, allowing the identification of ages with equivalent-risk in groups with different exposures. Most importantly, our results suggest that a substantial burden of sporadic diseases can be substantially delayed or avoided by early lifestyle interventions.