Seventy-five genetic loci influencing the human red blood cell

Summary, in English

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.

• Author: 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 Engström; 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; 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
• Department/s: Cardiovascular Research - Hypertension; Cardiovascular Research - Epidemiology; EXODIAB: Excellence of Diabetes Research in Sweden; EpiHealth: Epidemiology for Health
• Publishing year: 2012
• Language: English
• Pages: 369-375
• Publication/Series: Nature
• Volume: 492
• Issue: 7429
• Links: http://dx.doi.org/10.1038/nature11677
• Document type: Journal article
• Publisher: Nature Publishing Group
• Topic: Cardiac and Cardiovascular Systems
• Status: Published
• Research group: Cardiovascular Research - Hypertension; Cardiovascular Research - Epidemiology
• ISBN/ISSN/Other: ISSN: 0028-0836