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 only been modeled for monogenic (Mendelian) diseases. Here, we develop a MSDB model for complex disease susceptibility: we assume that genotype relates to disease risk according to the canonical liability threshold model and that selection on variants affecting risk derives from the fitness cost of the disease, and focus on diseases that are highly polygenic, entail a substantial fitness cost, and are neither extremely common in the population nor exceedingly rare. Contrasting model predictions

SUBMITTER: Berg JJ 

PROVIDER: S-EPMC12132567 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature