Seventy-five genetic loci influencing the human red blood cell

Pim van der Harst; Weihua Zhang; Irene Mateo Leach; Augusto Rendon; Niek Verweij; Joban Sehmi; Dirk S. Paul; Ulrich Elling; Hooman Allayee; Xinzhong Li; Aparna Radhakrishnan; Sian-Tsung Tan; Katrin Voss; Christian X. Weichenberger; Cornelis A. Albers; Abtehale Al-Hussani; Folkert W. Asselbergs; Marina Ciullo; Fabrice Danjou; Christian Dina; Tonu Esko; David M. Evans; Lude Franke; Martin Goegele; Jaana Hartiala; Micha Hersch; Hilma Holm; Jouke-Jan Hottenga; Stavroula Kanoni; Marcus E. Kleber; Vasiliki Lagou; Claudia Langenberg; Lorna M. Lopez; Leo-Pekka Lyytikainen; Olle Melander; Federico Murgia; Ilja M. Nolte; Paul F. O'Reilly; Sandosh Padmanabhan; Afshin Parsa; Nicola Pirastu; Eleonora Porcu; Laura Portas; Inga Prokopenko; Janina S. Ried; So-Youn Shin; Clara S. Tang; Alexander Teumer; Michela Traglia; Sheila Ulivi; Harm-Jan Westra; Jian Yang; Jing Hua Zhao; Franco Anni; Abdel Abdellaoui; Antony Attwood; Beverley Balkau; Stefania Bandinelli; Francois Bastardot; Beben Benyamin; Bernhard O. Boehm; William O. Cookson; Debashish Das; Paul I. W. de Bakker; Rudolf A. de Boer; Eco J. C. de Geus; Marleen H. de Moor; Maria Dimitriou; Francisco S. Domingues; Angela Doering; Gunnar Engstrom; Gudmundur Ingi Eyjolfsson; Luigi Ferrucci; Krista Fischer; Renzo Galanello; Stephen F. Garner; Bernd Genser; Quince D. Gibson; Giorgia Girotto; Daniel Fannar Gudbjartsson; Sarah E. Harris; Anna-Liisa Hartikainen; Claire E. Hastie; Bo Hedblad; Thomas Illig; Jennifer Jolley; Mika Kahonen; Ido P. Kema; John P. Kemp; Liming Liang; Heather Lloyd-Jones; Ruth J. F. Loos; Stuart Meacham; Sarah E. Medland; Christa Meisinger; Yasin Memari; Evelin Mihailov; Kathy Miller; Miriam F. Moffatt; Matthias Nauck; Maria Novatchkova; Teresa Nutile; Isleifur Olafsson; Pall T. Onundarson; Debora Parracciani; Brenda W. Penninx; Lucia Perseu; Antonio Piga; Giorgio Pistis; Anneli Pouta; Ursula Puc; Olli Raitakari; Susan M. Ring; Antonietta Robino; Daniela Ruggiero; Aimo Ruokonen; Aude Saint-Pierre; Cinzia Sala; Andres Salumets; Jennifer Sambrook; Hein Schepers; Carsten Oliver Schmidt; Herman H. W. Sillje; Rob Sladek; Johannes H. Smit; John M. Starr; Jonathan Stephens; Patrick Sulem; Toshiko Tanaka; Unnur Thorsteinsdottir; Vinicius Tragante; Wiek H. van Gilst; L. Joost van Pelt; Dirk J. van Veldhuisen; Uwe Voelker; John B. Whitfield; Gonneke Willemsen; Bernhard R. Winkelmann; Gerald Wirnsberger; Ale Algra; Francesco Cucca; Adamo Pio d'Adamo; John Danesh; Ian J. Deary; Anna F. Dominiczak; Paul Elliott; Paolo Fortina; Philippe Froguel; Paolo Gasparini; Andreas Greinacher; Stanley L. Hazen; Marjo-Riitta Jarvelin; Kay Tee Khaw; Terho Lehtimaki; Winfried Maerz; Nicholas G. Martin; Andres Metspalu; Braxton D. Mitchell; Grant W. Montgomery; Carmel Moore; Gerjan Navis; Mario Pirastu; Peter P. Pramstaller; Ramiro Ramirez-Solis; Eric Schadt; James Scott; Alan R. Shuldiner; George Davey Smith; J. Gustav Smith; Harold Snieder; Rossella Sorice; Tim D. Spector; Kari Stefansson; Michael Stumvoll; W. H. Wilson Tang; Daniela Toniolo; Anke Toenjes; Peter M. Visscher; Peter Vollenweider; Nicholas J. Wareham; Bruce H. R. Wolffenbuttel; Dorret I. Boomsma; Jacques S. Beckmann; George V. Dedoussis; Panos Deloukas; Manuel A. Ferreira; Serena Sanna; Manuela Uda; Andrew A. Hicks; Josef Martin Penninger; Christian Gieger; Jaspal S. Kooner; Willem H. Ouwehand; Nicole Soranzo; John C. Chambers

doi:10.1038/nature11677

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Seventy-five genetic loci influencing the human red blood cell

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Seventy-five genetic loci influencing the human red blood cell

Pim van der Harst, Weihua Zhang, Irene Mateo Leach, Augusto Rendon, Niek Verweij, Joban Sehmi, Dirk S. Paul, Ulrich Elling, Hooman Allayee, Xinzhong Li, …

Nature (London), Vol.492(7429), pp.369-75

20/12/2012

DOI: https://doi.org/10.1038/nature11677

PMCID: PMC3623669

PMID: 23222517

Abstract

Multidisciplinary Sciences

Science & Technology

Science & Technology - Other Topics

Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.

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Title: Seventy-five genetic loci influencing the human red blood cell
Creators - without role: Pim van der Harst - University Medical Center Groningen
Weihua Zhang - Ealing Hospital
Irene Mateo Leach - University of Groningen
Augusto Rendon - University of Cambridge
Niek Verweij - University Medical Center Groningen
Joban Sehmi - Imperial College London
Dirk S. Paul - Wellcome Sanger Institute
Ulrich Elling - Austrian Academy of Sciences
Hooman Allayee - University of Southern California
Xinzhong Li - Imperial College London
Aparna Radhakrishnan - University of Cambridge
Sian-Tsung Tan - Ealing Hospital NHS Trust
Katrin Voss - University of Cambridge
Christian X. Weichenberger - Eurac Research
Cornelis A. Albers - University of Cambridge
Abtehale Al-Hussani - Imperial College London
Folkert W. Asselbergs - University Medical Center Utrecht
Marina Ciullo - Institute of Genetics and Biophysics
Fabrice Danjou - Ospedale Microcitemico
Christian Dina - Inserm
Tonu Esko - University of Tartu
David M. Evans - University of Bristol
Lude Franke - University Medical Center Groningen
Martin Goegele - European Acad Bozen Bolzano EURAC, Ctr Biomed, I-39100 Bolzano, Italy
Jaana Hartiala - University of Southern California
Micha Hersch - SIB Swiss Institute of Bioinformatics
Hilma Holm - deCODE Genetics
Jouke-Jan Hottenga - University of Amsterdam
Stavroula Kanoni - Wellcome Sanger Institute
Marcus E. Kleber - University of Mannheim
Vasiliki Lagou - University of Oxford
Claudia Langenberg - MRC Epidemiology Unit
Lorna M. Lopez - University of Edinburgh
Leo-Pekka Lyytikainen - Fimlab
Olle Melander - Lund University
Federico Murgia - National Research Council
Ilja M. Nolte - University Medical Center Groningen
Paul F. O'Reilly - Imperial College London
Sandosh Padmanabhan - University of Glasgow
Afshin Parsa - University of Maryland, Baltimore
Nicola Pirastu - IRCCS Materno Infantile Burlo Garofolo
Eleonora Porcu - Institute of Genetic and Biomedical Research
Laura Portas - National Research Council
Inga Prokopenko - Oxford Centre for Diabetes, Endocrinology and Metabolism
Janina S. Ried - Helmholtz Zentrum München
So-Youn Shin - Wellcome Sanger Institute
Clara S. Tang - QIMR Berghofer Medical Research Institute
Alexander Teumer - Greifswald University Hospital
Michela Traglia - Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy
Sheila Ulivi - IRCCS Materno Infantile Burlo Garofolo
Harm-Jan Westra - University Medical Center Groningen
Jian Yang - Princess Alexandra Hospital
Jing Hua Zhao - MRC Epidemiology Unit
Franco Anni - Ospedale Microcitemico
Abdel Abdellaoui - University of Amsterdam
Antony Attwood - University of Cambridge
Beverley Balkau - Centre de recherche en Epidémiologie et Santé des Populations
Stefania Bandinelli - Azienda Sanitaria di Firenze
Francois Bastardot - University Hospital of Lausanne
Beben Benyamin - QIMR Berghofer Medical Research Institute
Bernhard O. Boehm - University Hospital Ulm
William O. Cookson - Imperial College London
Debashish Das - University College London
Paul I. W. de Bakker - University Medical Center Utrecht
Rudolf A. de Boer - University Medical Center Groningen
Eco J. C. de Geus - University of Amsterdam
Marleen H. de Moor - University of Amsterdam
Maria Dimitriou - Harokopio University of Athens
Francisco S. Domingues - Eurac Research
Angela Doering - Helmholtz Zentrum München
Gunnar Engstrom - Lund University
Gudmundur Ingi Eyjolfsson - Lab Mjodd, IS-108 Reykjavik, Iceland
Luigi Ferrucci - National Institute on Aging
Krista Fischer - University of Tartu
Renzo Galanello - Ospedale Microcitemico
Stephen F. Garner - University of Cambridge
Bernd Genser - University of Mannheim
Quince D. Gibson - University of Maryland, Baltimore
Giorgia Girotto - University of Trieste
Daniel Fannar Gudbjartsson - deCODE Genetics
Sarah E. Harris - University of Edinburgh
Anna-Liisa Hartikainen - University of Oulu
Claire E. Hastie - University of Glasgow
Bo Hedblad - Lund University
Thomas Illig - Helmholtz Zentrum München
Jennifer Jolley - University of Cambridge
Mika Kahonen - Tampere University Hospital
Ido P. Kema - University Medical Center Groningen
John P. Kemp - University of Bristol
Liming Liang - Harvard University
Heather Lloyd-Jones - University of Cambridge
Ruth J. F. Loos - MRC Epidemiology Unit
Stuart Meacham - University of Cambridge
Sarah E. Medland - QIMR Berghofer Medical Research Institute
Christa Meisinger - Helmholtz Zentrum München
Yasin Memari - Wellcome Sanger Institute
Evelin Mihailov - Institute of Genetics and Biophysics
Kathy Miller - Ealing Hospital
Miriam F. Moffatt - Imperial College London
Matthias Nauck - Greifswald University Hospital
Maria Novatchkova - Austrian Acad Sci, Inst Mol Biotechnol, A-1030 Vienna, Austria
Teresa Nutile - CNR, Inst Genet & Biophys Adriano Buzzati Traverso, I-80131 Naples, Italy
Isleifur Olafsson - Landspitali Univ Hosp, Dept Clin Biochem, IS-101 Reykjavik, Iceland
Pall T. Onundarson - University of Iceland
Debora Parracciani - Genet Pk Ogliastra, Perdasdefogu, Sardinia, Italy
Brenda W. Penninx - University of Amsterdam
Lucia Perseu - Cittadella Univ Monserrato, CNR, Ist Ric Genet & Biomed, I-09042 Cagliari, Italy
Antonio Piga - University of Turin
Giorgio Pistis - Mylan
Anneli Pouta - University of Oulu
Ursula Puc - Austrian Acad Sci, Inst Mol Biotechnol, A-1030 Vienna, Austria
Olli Raitakari - College Station Medical Center
Susan M. Ring - University of Bristol
Antonietta Robino - University of Trieste
Daniela Ruggiero - CNR, Inst Genet & Biophys Adriano Buzzati Traverso, I-80131 Naples, Italy
Aimo Ruokonen - University of Oulu
Aude Saint-Pierre - European Acad Bozen Bolzano EURAC, Ctr Biomed, I-39100 Bolzano, Italy
Cinzia Sala - Mylan
Andres Salumets - College Station Medical Center
Jennifer Sambrook - University of Cambridge
Hein Schepers - University of Groningen
Carsten Oliver Schmidt - College Station Medical Center
Herman H. W. Sillje - University of Groningen
Rob Sladek - McGill University
Johannes H. Smit - University of Amsterdam
John M. Starr - University of Edinburgh
Jonathan Stephens - University of Cambridge
Patrick Sulem - deCODE Genet, IS-101 Reykjavik, Iceland
Toshiko Tanaka - NIA, Clin Res Branch, Baltimore, MD 21250 USA
Unnur Thorsteinsdottir - deCODE Genet, IS-101 Reykjavik, Iceland
Vinicius Tragante - College Station Medical Center
Wiek H. van Gilst - University of Groningen
L. Joost van Pelt - University of Groningen
Dirk J. van Veldhuisen - University of Groningen
Uwe Voelker - College Station Medical Center
John B. Whitfield - College Station Medical Center
Gonneke Willemsen - University of Amsterdam
Bernhard R. Winkelmann - ClinPhen Study Ctr, D-60594 Frankfurt, Germany
Gerald Wirnsberger - Austrian Acad Sci, Inst Mol Biotechnol, A-1030 Vienna, Austria
Ale Algra - College Station Medical Center
Francesco Cucca - Cittadella Univ Monserrato, CNR, Ist Ric Genet & Biomed, I-09042 Cagliari, Italy
Adamo Pio d'Adamo - University of Trieste
John Danesh - University of Cambridge
Ian J. Deary - University of Edinburgh
Anna F. Dominiczak - University of Glasgow
Paul Elliott - University of London
Paolo Fortina - Thomas Jefferson University
Philippe Froguel - Queen Saovabha Memorial Institute
Paolo Gasparini - University of Trieste
Andreas Greinacher - College Station Medical Center
Stanley L. Hazen - Cleveland Clin, Lerner Res Inst, Dept Cell Biol, Ctr Cardiovasc Diagnost & Prevent, Cleveland, OH 44195 USA
Marjo-Riitta Jarvelin - University of London
Kay Tee Khaw - Addenbrookes Hosp, Clin Gerontol Unit, Cambridge CB2 2QQ, England
Terho Lehtimaki - Tampere University
Winfried Maerz - Heidelberg University
Nicholas G. Martin - College Station Medical Center
Andres Metspalu - University of Tartu
Braxton D. Mitchell - Supreme Council Of Health
Grant W. Montgomery - College Station Medical Center
Carmel Moore - University of Cambridge
Gerjan Navis - University of Groningen
Mario Pirastu - Natl Res Council Italy, Inst Populat Genet, I-07100 Sassari, Italy
Peter P. Pramstaller - European Acad Bozen Bolzano EURAC, Ctr Biomed, I-39100 Bolzano, Italy
Ramiro Ramirez-Solis - Wellcome Sanger Institute
Eric Schadt - Supreme Council Of Health
James Scott - University of London
Alan R. Shuldiner - Supreme Council Of Health
George Davey Smith - University of Bristol
J. Gustav Smith - Lund University
Harold Snieder - University of Groningen
Rossella Sorice - CNR, Inst Genet & Biophys Adriano Buzzati Traverso, I-80131 Naples, Italy
Tim D. Spector - Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England
Kari Stefansson - deCODE Genet, IS-101 Reykjavik, Iceland
Michael Stumvoll - College Station Medical Center
W. H. Wilson Tang - Cleveland Clin, Lerner Res Inst, Dept Cell Biol, Ctr Cardiovasc Diagnost & Prevent, Cleveland, OH 44195 USA
Daniela Toniolo - Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy
Anke Toenjes - College Station Medical Center
Peter M. Visscher - University of Edinburgh
Peter Vollenweider - University of Lausanne
Nicholas J. Wareham - Massachusetts Rehabilitation Commission
Bruce H. R. Wolffenbuttel - University of Groningen
Dorret I. Boomsma - University of Amsterdam
Jacques S. Beckmann - University of Lausanne
George V. Dedoussis - Harokopio University of Athens
Panos Deloukas - Wellcome Sanger Institute
Manuel A. Ferreira - College Station Medical Center
Serena Sanna - Cittadella Univ Monserrato, CNR, Ist Ric Genet & Biomed, I-09042 Cagliari, Italy
Manuela Uda - Cittadella Univ Monserrato, CNR, Ist Ric Genet & Biomed, I-09042 Cagliari, Italy
Andrew A. Hicks - European Acad Bozen Bolzano EURAC, Ctr Biomed, I-39100 Bolzano, Italy
Josef Martin Penninger - Austrian Acad Sci, Inst Mol Biotechnol, A-1030 Vienna, Austria
Christian Gieger - Helmholtz Zentrum München
Jaspal S. Kooner - Ealing Hosp NHS Trust, Uxbridge UB1 3HW, Middx, England
Willem H. Ouwehand - University of Cambridge
Nicole Soranzo - Wellcome Sanger Institute
John C. Chambers - University of London
Publication Details: Nature (London), Vol.492(7429), pp.369-75
Publisher: Springer Nature
Number of pages: 9
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UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission R01HD042157 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) I 434 / Austrian Science Fund FWF; Austrian Science Fund (FWF) G0401527; MC_U106188470; G0700704; G1000143; G0801056; MC_U106179471; G1002084; G0600705; G9815508 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission 14136 / Cancer Research UK R01 AG018728; N01AG12109 / NIA NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) R01 GM053275; U01 GM074518 / NIGMS NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) 092731; 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Identifiers: 9940056608331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article