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

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.369-375

20/12/2012

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

PMID: 23222517

Abstract

Multidisciplinary Sciences

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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: Pim van der Harst - University Medical Center Groningen
Weihua Zhang - Imperial College London
Irene Mateo Leach - University Medical Center Groningen
Augusto Rendon - University of Cambridge
Niek Verweij - University Medical Center Groningen
Joban Sehmi - Ealing Hospital
Dirk S. Paul - Wellcome Sanger Institute
Ulrich Elling - Austrian Academy of Sciences
Hooman Allayee - University of Southern California
Xinzhong Li - University of London
Aparna Radhakrishnan - University of Cambridge
Sian-Tsung Tan - Ealing Hospital
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 of Groningen
Martin Goegele - European Acad Bozen Bolzano EURAC, Ctr Biomed, I-39100 Bolzano, Italy
Jaana Hartiala - University of Southern California
Micha Hersch - University of Lausanne
Hilma Holm - deCODE Genetics
Jouke-Jan Hottenga - University of Amsterdam
Stavroula Kanoni - Wellcome Sanger Institute
Marcus E. Kleber - University of Mannheim
Vasiliki Lagou - Oxford Centre for Diabetes, Endocrinology and Metabolism
Claudia Langenberg - MRC Epidemiology Unit
Lorna M. Lopez - University of Edinburgh
Leo-Pekka Lyytikainen - Tampere University
Olle Melander - Lund University
Federico Murgia - National Research Council
Ilja M. Nolte - University Medical Center Groningen
Paul F. O'Reilly - University of 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 - Universitätsmedizin Greifswald
Michela Traglia - Mylan
Sheila Ulivi - IRCCS Materno Infantile Burlo Garofolo
Harm-Jan Westra - University of Groningen
Jian Yang - Princess Alexandra Hospital
Jing Hua Zhao - Massachusetts Rehabilitation Commission
Franco Anni - Ospedale Microcitemico
Abdel Abdellaoui - Vrije Universiteit 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 - Vrije Universiteit Amsterdam
Marleen H. de Moor - Vrije Universiteit 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 - IRCCS Materno Infantile Burlo Garofolo
Daniel Fannar Gudbjartsson - deCODE Genet, IS-101 Reykjavik, Iceland
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 - Wellcome Sanger Institute
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 - Universitätsmedizin Greifswald
Publication Details: Nature (London), Vol.492(7429), pp.369-375
Publisher: Springer Nature
Number of pages: 9
Date published: 20/12/2012
Grant note: R01 HD042157 / NICHD NIH HHS; 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) P30 DK072488 / NIDDK NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) P30DK072488 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) R01LM010098 / NATIONAL LIBRARY OF MEDICINE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Library of Medicine (NLM) U01 HG004402 / NHGRI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI) G0801056B / Medical Research Council; 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
Identifiers: 99928767902346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

Seventy-five genetic loci influencing the human red blood cell

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