Extensive antagonistic variants across the human genome

Abstract Pleiotropic conflict, where a genetic locus has antagonistic effects on different traits, is a common phenomenon observed in animals and plants. While pleiotropy has been widely reported in humans, there is no systematic study of pleiotropic conflict in humans. Here, we leverage GWAS summary statistics of complex diseases and traits derived from large-scale population cohorts to identify pleiotropic regions with conflicting effects. Through a multi-trait colocalization approach, we identified 219 independent regions containing variants showing pleiotropic conflict, which cover ∼11.4% of linkage disequilibrium blocks in the human genome. Antagonistic variants are observed to be enriched for SNPs with intermediate minor allele frequencies and antagonistic regions show signatures of positive/balancing selection. Our results suggest that antagonistic variants are pervasive in humans and indicate their role in maintaining phenotypic and genetic diversity in humans.