The Polygenic and Monogenic Basis of Blood Traits and Diseases
Fotios Koskeridis; Ruth J.F. Loos; Ming-Huei Chen; Alan B. Zonderman; Andreas Greinacher; James S. Floyd; Jeff Haessler; Stephan B. Felix; Huijun Qian; Laura M. Raffield; Stephen B. Watt; Jonathan D. Rosen; Manuel Tardaguila; Christopher J. Penkett; Praveen Surendran; Saori Sakaue; Henry Völzke; Parsa Akbari; Michel Georges; Yukinori Okada; Jennifer E. Huffman; Kumaraswamy N. Chitrala; Ani Manichaikul; Kjell Nikus; Uwe Völker; Andrew D. Johnson; Michele K. Evans; Hélène Choquet; Wei Huang; Regina Manansala; Nathan Pankratz; Jean-Claude Tardif; Paul Elliott; Yongmei Liu; Petra Schubert; Patrick K. Albers; Na Cai; Hannes Ponsting; Erwin P. Bottinger; Traci M. Bartz; Allan Linneberg; Nicholas A. Watkins; Oliver Stegle; Yoav Ben-Shlomo; Bruce M. Psaty; Benjamin A.T. Rodriguez; Kousik Kundu; Scott C. Ritchie; Frank J.A.van Rooij; Ken Sin Lo; Masahiro Kanai; Karyn Megy; Koichi Matsuda; Olli T. Raitakari; Stephen S. Rich; Girish N. Nadkarni; Klaudia Walter; Leslie A. Lange; Peter W.F. Wilson; Niki Dimou; Jette Bork-Jensen; Michael Preuss; Alexander P. Reiner; Michael H. Guo; Torben Hansen; Cassandra N. Spracklen; Michael Inouye; Guillaume Lettre; Karen L. Mohlke; Tao Jiang; Leo-Pekka Lyytikäinen; Joanna M.M. Howson; Vijay G. Sankaran; Tõnu Esko; Oluf Pedersen; Linda Broer; Jerome I. Rotter; Terho Lehtimäki; Tim Kacprowski; Paul L. Auer; Mika Kähönen; Qi Guo; Savita Karthikeyan; Mohsen Ghanbari; Jingzhong Ding; Emanuele Di Angelantonio; Willem H. Ouwehand; Niels Grarup; Erik L. Bao; Abdou Mousas; Hua Tang; Nicole Soranzo; VA Million Veteran Program; Masato Akiyama; William J. Astle; Yun Li; Emilie M. Wigdor; Evangelos Evangelou; Stefan Weiss; Kelly Cho; Andrew Beswick; Eric Jorgenson; Yoshinori Murakami; Arden Moscati; Yoichiro Kamatani; Caleb A. Lareau; Nina Mononen; John Danesh; Adam S. Butterworth; Julian C. Knight; Jennifer A. Brody; David J. Roberts; Dragana Vuckovic
https://urn.fi/URN:NBN:fi-fe2021042822484
Tiivistelmä
Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation.
Kokoelmat
- Rinnakkaistallenteet [19207]