The Polygenic and Monogenic Basis of Blood Traits and Diseases
Dragana Vuckovic(University of Cambridge), Erik L. Bao(Broad Institute), Parsa Akbari(University of Cambridge), Caleb A. Lareau(Broad Institute), Abdou Mousas(Montreal Heart Institute), Tao Jiang(University of Cambridge), Ming‐Huei Chen(National Heart Lung and Blood Institute), Laura M. Raffield(University of North Carolina at Chapel Hill), Manuel Tardáguila(Wellcome Sanger Institute), Jennifer E. Huffman(VA Boston Healthcare System), Scott C. Ritchie(Baker Heart and Diabetes Institute), Karyn Mégy(National Health Service), Hannes Ponstingl(Wellcome Sanger Institute), Christopher J. Penkett(University of Cambridge), Patrick K. Albers(Wellcome Sanger Institute), Emilie M. Wigdor(Wellcome Sanger Institute), Saori Sakaue(RIKEN Center for Integrative Medical Sciences), Arden Moscati(Icahn School of Medicine at Mount Sinai), Regina Manansala(University of Wisconsin–Milwaukee), Ken Sin Lo(Montreal Heart Institute), Huijun Qian(University of North Carolina at Chapel Hill), Masato Akiyama(Kyushu University), Traci M. Bartz(University of Washington), Yoav Ben‐Shlomo(University of Bristol), Andrew D Beswick(University of Bristol), Jette Bork‐Jensen(University of Copenhagen), Erwin P. Böttinger(Hasso Plattner Institute), Jennifer A. Brody(University of Washington), Frank J.A. van Rooij(Erasmus MC), Kumaraswamy Naidu Chitrala(National Institute on Aging), Peter W.F. Wilson(Atlanta VA Medical Center), Hélène Choquet(Kaiser Permanente), John Danesh(University of Cambridge), Emanuele Di Angelantonio(University of Cambridge), Niki Dimou(University of Ioannina), Jingzhong Ding(Wake Forest University), Paul Elliott(Imperial College Healthcare NHS Trust), Tõnu Esko(Broad Institute), Michele K. Evans(National Institute on Aging), Stephan B. Felix(Universitätsmedizin Greifswald), James S. Floyd(University of Washington), Linda Broer(Erasmus MC), Niels Grarup(University of Copenhagen), Michael H. Guo(Broad Institute), Qi Guo(University of Cambridge), Andreas Greinacher(Universitätsmedizin Greifswald), Jeff Haessler(Fred Hutch Cancer Center), Torben Hansen(University of Copenhagen), Joanna M. M. Howson(University of Cambridge), Wei Huang(Chinese National Human Genome Center), Eric Jorgenson(Kaiser Permanente), Tim Kacprowski(Universitätsmedizin Greifswald), Mika Kähönen(Tampere University), Yoichiro Kamatani(RIKEN Center for Integrative Medical Sciences), Masahiro Kanai(Massachusetts General Hospital), Savita Karthikeyan(University of Cambridge), Fotios Koskeridis(University of Ioannina), Leslie A. Lange(University of Colorado Anschutz Medical Campus), Terho Lehtimäki(Tampere University of Applied Sciences), Allan Linneberg(University of Copenhagen), Yongmei Liu(Duke Medical Center), Leo‐Pekka Lyytikäinen(Tampere University of Applied Sciences), Ani Manichaikul(University of Virginia), Koichi Matsuda(The University of Tokyo), Karen L. Mohlke(University of North Carolina at Chapel Hill), Nina Mononen(Tampere University of Applied Sciences), Yoshinori Murakami(The University of Tokyo), Girish N. Nadkarni(Icahn School of Medicine at Mount Sinai), Kjell Nikus(Tampere University), Nathan Pankratz(University of Minnesota), Oluf Pedersen(University of Copenhagen), Michael Preuß(Icahn School of Medicine at Mount Sinai), Bruce M. Psaty(Kaiser Permanente Washington Health Research Institute), Olli T. Raitakari(University of Turku), Stephen S. Rich(University of Virginia), Blanca Rodríguez(National Heart Lung and Blood Institute), Jonathan D. Rosen(University of North Carolina at Chapel Hill), Jerome I. Rotter(The Lundquist Institute), Petra Schubert(VA Boston Healthcare System), Cassandra N. Spracklen(University of North Carolina at Chapel Hill), Praveen Surendran(University of Cambridge), Hua Tang(Stanford University), Jean‐Claude Tardif(Montreal Heart Institute), Mohsen Ghanbari(Mashhad University of Medical Sciences), Uwe Völker(Universitätsmedizin Greifswald), Henry Völzke(Universitätsmedizin Greifswald), Nicholas A. Watkins(National Health Service), Stefan Weiß(Universitätsmedizin Greifswald), Na Cai(Wellcome Sanger Institute), Kousik Kundu(University of Cambridge), Stephen B. Watt(Wellcome Sanger Institute), Klaudia Walter(Wellcome Sanger Institute), Alan B. Zonderman(National Institute on Aging), Kelly Cho(Brigham and Women's Hospital), Yun Li(University of North Carolina at Chapel Hill), Ruth J. F. Loos(Icahn School of Medicine at Mount Sinai), Julian C. Knight(Centre for Human Genetics), Michel Georges(University of Liège), Oliver Stegle(European Bioinformatics Institute), Εvangelos Εvangelou(University of Ioannina), Yukinori Okada(The University of Osaka), David J. Roberts(NHS Blood and Transplant), Michael Inouye(Turing Institute), Andrew D. Johnson(National Heart Lung and Blood Institute), Paul L. Auer(University of Wisconsin–Milwaukee), William J. Astle(National Health Service), Alex P. Reiner(University of Washington), Adam S. Butterworth(University of Cambridge), Willem H. Ouwehand(National Health Service), Guillaume Lettre(Montreal Heart Institute), Vijay G. Sankaran(Broad Institute), Nicole Soranzo(University of Cambridge)
Cited by 738Open Access
Abstract
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.
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