The impact of background selection in mutation-selection-drift balance models of complex trait evolution.

Over the past three decades, theoretical population genetic models and empirical analyses have elaborated on how the elimination of deleterious variants reduces variation at linked neutral sites. This process is known as background selection. However, the impact of background selection has been studied almost exclusively without reference to its effect on phenotypic variation. Here, we use population genetic theory and simulation to investigate the consequences of background selection for linked variation impacting complex traits. We find the impact of background selection on a complex trait depends on the type of selection acting on the trait, the effect size distribution, and the background selection intensity. For instance, background selection impacts a much broader range of effect sizes for traits under directional selection via a liability threshold mechanism (i.e. when selection acts on individuals with phenotypes exceeding a threshold) than when fitness decays exponentially with trait value. We also find that background selection can increase the population prevalence of a liability threshold trait (e.g. a complex binary disease trait). Furthermore, while background selection can only reduce the genetic variance of a trait under directional selection (as might be expected from the classical population genetic theory for linked neutral variants) we find that background selection can increase the genetic variance of a trait under stabilizing selection. The results presented here use a synthesis of population genetic and quantitative genetic modeling, and overall, have relevance for understand the genetic architecture and evolution of complex traits, including complex diseases.