Mutation-selection-drift balance models of complex diseases.

ABSTRACT: Genetic variation that influences complex disease susceptibility is introduced into the population by mutation and removed by natural selection and genetic drift. This mutation-selection-drift balance (MSDB) shapes the prevalence of a disease and its genetic architecture. To date, however, MSDB has been modeled only for monogenic (Mendelian) diseases. Here, we develop an MSDB model for complex disease susceptibility: we assume that genotype relates to disease risk according to the canonical liability threshold model and that the selection on variants affecting risk stems from the fitness cost of the disease. We focus on diseases that are highly polygenic, entail a substantial fitness cost, and are neither extremely common in the population nor exceedingly rare. The comparison of model pred

SUBMITTER: Berg JJ 

PROVIDER: S-EPMC12693578 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature