How much disease risk is due to old age and established risk factors?

Improved healthcare is leading to older populations and increasing numbers of individuals experiencing multiple diseases, possibly concurrently (multimorbidity). This article asks whether the observed number of new diseases is more than expected based on age and established risk factors alone, assuming that disease risk is unchanged by prior or pre-existing disease. This is accomplished by designing a new epidemiological approach, where the expected number of disease types are estimated for individuals without prior disease, by combining individual risk predictions with a "Poisson-Binomial" model to estimate the expected number of new diseases and its confidence interval. For 123 diseases in men and 99 diseases in women, the expected number of new diseases based on age and established risk factors was approximately $$ of that observed, with the observed number of new diseases approximately $$ times that predicted. The differences could not be explained by natural statistical variation, and provide a rigorous statistical demonstration of lower disease risk for individuals without any previous disease. The multiple of $$ was sufficiently consistent across different diseases to prevent its use for classification of disease types, but there were differences for subgroups such as smokers with high body mass index, and for some classes of disease (as defined by the International Classification of Diseases, version 10). The results suggest that empirical modeling might allow reliable predictions of future hospital admissions, and confirm the value of conventional epidemiological approaches that study disease risk in healthy individuals. The implications and future possibilities of this new approach are discussed.