title: 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.
authors.affiliation: Gruppo Interdipartimentale di Bioinformatica e Biologia Computazionale, Università di Napoli Federico II-Università di Salerno, Naples, Italy. roamato@na.infn.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Amato
authors.forename: Gennaro
authors.initials: G
authors.lastname: Miele
authors.forename: Antonella
authors.initials: A
authors.lastname: Monticelli
authors.forename: Sergio
authors.initials: S
authors.lastname: Cocozza
mesh_terms: D001827:Body Height / Q000235:genetics*; D005787:Gene Frequency; D005828:Genetics, Population; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008962:Models, Theoretical; D020412:Multifactorial Inheritance / Q000235:genetics; D012641:Selection, Genetic / Q000235:genetics*
references.citation: Nat Rev Genet. 2009 Sep;10(9):639-50
references.pmid: 19687804
references.citation: Nat Rev Genet. 2010 Oct;11(10):665-7
references.pmid: 20838407
references.citation: PLoS One. 2009 Nov 20;4(11):e7927
references.pmid: 19936260
references.citation: Nat Rev Genet. 2010 Sep;11(9):611-22
references.pmid: 20680024
references.citation: Science. 2006 Jun 16;312(5780):1614-20
references.pmid: 16778047
references.citation: Proc Biol Sci. 2002 Sep 22;269(1503):1919-23
references.pmid: 12350254
references.citation: Evolution. 2006 Nov;60(11):2226-38
references.pmid: 17236416
references.citation: Nature. 2000 Jan 13;403(6766):156
references.pmid: 10646589
references.citation: Nature. 2010 Oct 14;467(7317):832-8
references.pmid: 20881960
references.citation: Hum Nat. 2002 Dec;13(4):473-91
references.pmid: 26193091
references.citation: Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics. 2000 Nov;62(5 Pt B):7065-9
references.pmid: 11102062
references.citation: Nat Rev Genet. 2007 Nov;8(11):857-68
references.pmid: 17943193
references.citation: Curr Biol. 2010 Feb 23;20(4):R208-15
references.pmid: 20178769
references.citation: Philos Trans R Soc Lond B Biol Sci. 2010 Aug 27;365(1552):2459-68
references.pmid: 20643735