Maintenance of Complex Trait Variation: Classic Theory and Modern Data

Area of Science:

• Evolutionary genetics
• Population genetics
• Genomics

Background:

• Genome-wide association studies (GWAS) consistently detect negative selection acting on genetic loci.
• Selection intensity correlates with variant effect size, but pleiotropy complicates this relationship.
• Understanding selection requires models balancing direct and indirect (pleiotropic) effects on traits.

Purpose of the Study:

• To review theories of phenotypic and locus-specific selection.
• To discuss geometric theories of pleiotropic selection for future modeling.
• To integrate findings on pleiotropic genetic variation and population-specific effect sizes.

Main Methods:

• Review of classic and recent theories of selection.
• Analysis of existing GWAS data on negative selection.
• Discussion of geometric models for pleiotropic selection.

Main Results:

• Negative selection is evident at GWAS loci, intensifying with effect size.
• A significant pleiotropic component influences selection, acting beyond focal traits.
• Pleiotropic genetic variation and population-specific effect sizes impact selection inference.

Conclusions:

• Advanced models are necessary to balance multiple selection components.
• Incorporating pleiotropy and population dynamics is crucial for accurate selection analysis.
• GWAS effect sizes may be misleading if they vary across populations and time.