Abstract
Abstract
Horizontal pleiotropy, where one variant has independent effects on multiple traits, is important for our understanding of the genetic architecture of human phenotypes. We develop a method to quantify horizontal pleiotropy using genome-wide association summary statistics and apply it to 372 heritable phenotypes measured in 361,194 UK Biobank individuals. Horizontal pleiotropy is pervasive throughout the human genome, prominent among highly polygenic phenotypes, and enriched in active regulatory regions. Our results highlight the central role horizontal pleiotropy plays in the genetic architecture of human phenotypes. The HOrizontal Pleiotropy Score (HOPS) method is available on Github at https://github.com/rondolab/HOPS.
Funder
National Institute of General Medical Sciences
National Heart, Lung, and Blood Institute
American Heart Association
Publisher
Springer Science and Business Media LLC
Reference72 articles.
1. Zhan J, Arking DE, Bader JS. Discovering patterns of pleiotropy in genome-wide association studies. bioRxiv. 2018;28:273540.
2. Chesmore K, Bartlett J, Williams SM. The ubiquity of pleiotropy in human disease. Hum Genet. 2017;21:1–6.
3. Socrates A, Bond T, Karhunen V, Auvinen J, Rietveld C, Veijola J, et al. Polygenic risk scores applied to a single cohort reveal pleiotropy among hundreds of human phenotypes. bioRxiv. 2017;14:203257.
4. Solovieff N, Cotsapas C, Lee PH, Purcell SM, Smoller JW. Pleiotropy in complex traits: challenges and strategies. Nat Rev Genet. 2013;14(7):483–95.
5. Keightley PD, Hill WG. Variation maintained in quantitative traits with mutation–selection balance: pleiotropic side-effects on fitness traits. Proc R Soc Lond B. 1990;242(1304):95–100.
Cited by
47 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献