Seventy-five genetic loci influencing the human red blood cell.

Authors:
Dr. Ramiro Ramirez-Solis, PhD
Dr. Ramiro Ramirez-Solis, PhD
The Wellcome Trust Sanger Institute
Head of Mouse Pipelines
United Kingdom
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 Tõnu Esko David M Evans Lude Franke Martin Gögele Jaana Hartiala Micha Hersch Hilma Holm Jouke-Jan Hottenga Stavroula Kanoni Marcus E Kleber Vasiliki Lagou Claudia Langenberg Lorna M Lopez Leo-Pekka Lyytikäinen 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 François 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 Döring 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 Kähönen 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 Silljé 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 Völker 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 Lehtimäki Winfried Maerz Nicholas G Martin Andres Metspalu Braxton D Mitchell Grant W Montgomery Carmel Moore Gerjan Navis Mario Pirastu Peter P Pramstaller 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 Tönjes 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

Nature 2012 Dec 5;492(7429):369-75. Epub 2012 Dec 5.

Department of Cardiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.

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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http://dx.doi.org/10.1038/nature11677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623669PMC
December 2012
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