The Polygenic and Monogenic Basis of Blood Traits and Diseases | Zendy

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The Polygenic and Monogenic Basis of Blood Traits and Diseases

Author(s) -

Dragana Vuckovic,

Erik L. Bao,

Parsa Akbari,

Caleb A. Lareau,

Abdou Mousas,

Tao Jiang,

MingHuei Chen,

Laura M. Raffield,

Manuel Tardáguila,

Jennifer E. Huffman,

Scott C. Ritchie,

Karyn Mégy,

Hannes Ponstingl,

Christopher J. Penkett,

Patrick K. Albers,

Emilie M. Wigdor,

Saori Sakaue,

Arden Moscati,

Regina Manansala,

Ken Sin Lo,

Huijun Qian,

Masato Akiyama,

Traci M. Bartz,

Yoav BenShlomo,

Andrew D Beswick,

Jette BorkJensen,

Erwin P. Böttinger,

Jennifer A. Brody,

Frank J.A. van Rooij,

Kumaraswamy Naidu Chitrala,

Peter W.F. Wilson,

Hélène Choquet,

John Danesh,

Emanuele Di Angelantonio,

Niki Dimou,

Jingzhong Ding,

Paul Elliott,

Tõnu Esko,

Michele K. Evans,

Stephan B. Felix,

James S. Floyd,

Linda Broer,

Niels Grarup,

Michael H. Guo,

Qi Guo,

Andreas Greinacher,

Jeff Haessler,

Torben Hansen,

Joanna M. M. Howson,

Wei Huang,

Eric Jorgenson,

Tim Kacprowski,

Mika Kähönen,

Yoichiro Kamatani,

Masahiro Kanai,

Savita Karthikeyan,

Fotios Koskeridis,

Leslie A. Lange,

Terho Lehtimäki,

Allan Linneberg,

Yongmei Liu,

LeoPekka Lyytikäinen,

Ani Manichaikul,

Koichi Matsuda,

Karen L. Mohlke,

Nina Mon,

Yoshinori Murakami,

Girish N. Nadkarni,

Kjell Nikus,

Nathan Pankratz,

Oluf Pedersen,

Michael Preuß,

Bruce M. Psaty,

Olli T. Raitakari,

Stephen S. Rich,

Blanca Rodríguez,

Jonathan D. Rosen,

Jerome I. Rotter,

Petra Schubert,

Cassandra N. Spracklen,

Praveen Surendran,

Hua Tang,

JeanClaude Tardif,

Mohsen Ghanbari,

Uwe Völker,

Henry Völzke,

Nicholas A. Watkins,

Stefan Weiß,

Na Cai,

Kousik Kundu,

Stephen B. Watt,

Klaudia Walter,

Alan B. Zonderman,

Kelly Cho,

Yun Li,

Ruth J. F. Loos,

Julian C. Knight,

Michel Georges,

Oliver Stegle,

Εvangelos Εvangelou,

Yukinori Okada,

David J. Roberts,

Michael Inouye,

Andrew D. Johnson,

Paul L. Auer,

William J. Astle,

Alexander P. Reiner,

Adam S. Butterworth,

Willem H. Ouwehand,

Guillaume Lettre,

Vijay G. Sankaran,

Nicole Soranzo

Publication year - 2020

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2020.08.008

Subject(s) - biology , biobank , genome wide association study , genetic architecture , quantitative trait locus , mendelian inheritance , human genetic variation , genetic association , phenotype , human genetics , genetics , allele , genetic variation , computational biology , polygene , evolutionary biology , gene , single nucleotide polymorphism , genome , genotype , human genome

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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