PT - JOURNAL ARTICLE AU - Daniel M. Jordan AU - Marie Verbanck AU - Ron Do TI - Pervasive horizontal pleiotropy in human genetic variation is driven by extreme polygenicity of human traits and diseases AID - 10.1101/311332 DP - 2019 Jan 01 TA - bioRxiv PG - 311332 4099 - http://biorxiv.org/content/early/2019/08/13/311332.short 4100 - http://biorxiv.org/content/early/2019/08/13/311332.full AB - Horizontal pleiotropy, where one variant has independent effects on multiple traits, is important for our understanding of the genetic architecture of human phenotypes. We developed a method to quantify horizontal pleiotropy using genome-wide association summary statistics and applied it to 372 heritable phenotypes measured in 361,194 UK Biobank individuals. We observed horizontal pleiotropy is: 1) pervasive throughout the human genome; 2) especially prominent among highly polygenic phenotypes; 3) detected in 24,968 variants in 7,831 loci; and 4) enriched in active regulatory regions. Our results highlight the central role horizontal pleiotropy plays in the genetic architecture of human phenotypes.