How inherited variation shapes human disease trajectories

Although inherited variation is fixed at birth, its effects on health change with age and differ between common and rare variants. Here, we introduce Mendelnoulli, a longitudinal model that combines the age-dependent effects of polygenic and monogenic variation on health records, separating how much disease each individual accumulates overall from diseases to which they are prone. Mendelnoulli further allows polygenic and monogenic components to exert different influences on latent disease trajectories. We apply the model to 348 diseases, 36 polygenic scores, and 34 monogenic conditions across

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