The impact of population demography and selection on the genetic architecture of complex traits
Kirk E. Lohmueller
(Submitted on 21 Jun 2013)

Studies of thousands of individuals have found genetic evidence for dramatic population growth in recent human history. These studies have also documents high numbers of amino acid changing polymorphisms that are likely evolutionarily important and may be of medic relevance. Here I use population genetic models to demonstrate how the recent population growth has directly led to the accumulation of deleterious amino acid changing polymorphism. I show that recent growth increases the proportion of non synonymous SNPs and that the average mutation is more deleterious in an expanding population than in a non-exanded population. However, population growth does not affect the genetic load of the population. Additionally, I investigate the consequences of recent population growth on the architecture of complex traits. If a mutation’s effect on disease status is correlated with its effect on fitness, then rare variants explain a greater portion of the additive genetic variance of the trait in a population that has recently expanded than in a population that did not recently expand. Further, recent growth can increase the expected number of causal variants for a disease. Such heterogeneity will likely reduce the power of commonly used rare variants association tests. Finally, recent population growth also reduces the causal allele frequency in cases at single mutations, which could decrease the power of single-marker association tests. These findings suggest careful consideration of recent population history will be essential for designing optimal association studies for low-frequency and rare variants.