Extensive antagonistic variants across the human genome.

Area of Science:

• Human genetics
• Evolutionary biology
• Population genetics

Background:

• Pleiotropic conflict, where a single gene influences multiple traits antagonistically, is a known phenomenon in various organisms.
• While pleiotropy is documented in humans, systematic studies on pleiotropic conflict are lacking.

Purpose of the Study:

• To systematically identify regions in the human genome exhibiting pleiotropic conflict.
• To investigate the characteristics and evolutionary implications of these antagonistic variants.

Main Methods:

• Utilized summary statistics from large-scale genome-wide association studies (GWAS) of complex human diseases and traits.
• Employed a multi-trait colocalization approach to detect variants with conflicting effects across different traits.

Main Results:

• Identified 219 independent genomic regions associated with pleiotropic conflict, encompassing approximately 11.4% of human linkage disequilibrium blocks.
• Observed an enrichment of antagonistic variants with intermediate minor allele frequencies.
• Detected signatures of positive or balancing selection in these antagonistic regions.

Conclusions:

• Antagonistic pleiotropy is widespread in the human genome.
• These findings highlight the significant role of pleiotropic conflict in shaping human phenotypic and genetic diversity.