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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

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
Katso/Avaa
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Lataukset: 

Cell Press
doi:10.1016/j.cell.2020.08.008
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Julkaisun pysyvä osoite on:
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.

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