Signs of selective pressure on genetic variants affecting human height

Abstract

Many decades of scientific investigation have proved the role of selective pressure in Homo Sapiens at least at the level of individual genes or loci. Nevertheless, there are examples of polygenic traits that are bound to be under selection, but studies devoted to apply population genetics methods to unveil such occurrence are still lacking. Stature provides a relevant example of well-studied polygenic trait for which is now available a genome-wide association study which has identified the genes involved in this trait, and which is known to be under selection. We studied the behavior of F(ST) in a simulated toy model to detect population differentiation on a generic polygenic phenotype under selection. The simulations showed that the set of alleles involved in the trait has a higher mean F(ST) value than those undergoing genetic drift only. In view of this we looked for an increase in the mean F(ST) value of the 180 variants associated to human height. For this set of alleles we found F(ST) to be significantly higher than the genomic background (p = 0.0356). On the basis of a statistical analysis we excluded that the increase was just due to the presence of outliers. We also proved as marginal the role played by local adaptation phenomena, even on different phenotypes in linkage disequilibrium with genetic variants involved in height. The increase of F(ST) for the set of alleles involved in a polygenic trait seems to provide an example of symmetry breaking phenomenon concerning the population differentiation. The splitting in the allele frequencies would be driven by the initial conditions in the population dynamics which are stochastically modified by events like drift, bottlenecks, etc, and other stochastic events like the born of new mutations.

Figure 1. F_ST density distribution for the genomic background and the height associated variants.

Green lines mark the 5^th and 95^th percentiles of the genomic distribution.

Figure 2. Variants associated to height with high iHS score.

Red squares indicate mark the population in which the iHS score for the variant falls in the top 5^th percentile of the respective distribution.