Seventy-five genetic loci influencing the human red blood cell by van der Harst Pim, Zhang Weihua, Mateo Leach Irene, Rendon Augusto, Verweij Niek, Sehmi Joban, Paul Dirk S, Elling Ulrich, Allayee Hooman, Li Xinzhong, Radhakrishnan Aparna, Tan Sian-Tsung, Voss Katrin, Weichenberger Christian X, Albers Cornelis A, Al-Hussani Abtehale, Asselbergs Folkert W, Ciullo Marina, Danjou Fabrice, Dina Christian, Esko Tõnu, Evans David M, Franke Lude, Gögele Martin, Hartiala Jaana, Hersch Micha, Holm Hilma, Hottenga Jouke-Jan, Kanoni Stavroula, Kleber Marcus E, Lagou Vasiliki, Langenberg Claudia, Lopez Lorna M, Lyytikäinen Leo-Pekka, Melander Olle, Murgia Federico, Nolte Ilja M, O'Reilly Paul F, Padmanabhan Sandosh, Parsa Afshin, Pirastu Nicola, Porcu Eleonora, Portas Laura, Prokopenko Inga, Ried Janina S, Shin So-Youn, Tang Clara S, Teumer Alexander, Traglia Michela, Ulivi Sheila, Westra Harm-Jan, Yang Jian, Hua Zhao Jing, Anni Franco, Abdellaoui Abdel, Attwood Antony, Balkau Beverley, Bandinelli Stefania, Bastardot François, Benyamin Beben, Boehm Bernhard O, Cookson William O, Das Debashish, de Bakker Paul I W, de Boer Rudolf A, de Geus Eco J C, de Moor Marleen H, Dimitriou Maria, Domingues Francisco S, Döring Angela, Engström Gunnar, Ingi Eyjolfsson Gudmundur, Ferrucci Luigi, Fischer Krista, Galanello Renzo, Garner Stephen F, Genser Bernd, Gibson Quince D, Girotto Giorgia, Fannar Gudbjartsson Daniel, Harris Sarah E, Hartikainen Anna-Liisa, Hastie Claire E, Hedblad Bo, Illig Thomas, Jolley Jennifer, Kähönen Mika, Kema Ido P, Kemp John P, Liang Liming, Lloyd-Jones Heather, Loos Ruth J F, Meacham Stuart, Medland Sarah E, Meisinger Christa, Memari Yasin, Mihailov Evelin, Miller Kathy, Moffatt Miriam F, Nauck Matthias, Novatchkova Maria, Nutile Teresa, Olafsson Isleifur, Onundarson Pall T, Parracciani Debora, Penninx Brenda W, Perseu Lucia, Piga Antonio, Pistis Giorgio, Pouta Anneli, Puc Ursula, Raitakari Olli, Ring Susan M, Robino Antonietta, Ruggiero Daniela, Ruokonen Aimo, Saint-Pierre Aude, Sala Cinzia, Salumets Andres, Sambrook Jennifer, Schepers Hein, Oliver Schmidt Carsten, Silljé Herman H W, Sladek Rob, Smit Johannes H, Starr John M, Stephens Jonathan, Sulem Patrick, Tanaka Toshiko, Thorsteinsdottir Unnur, Tragante Vinicius, van Gilst Wiek H, Joost van Pelt L, van Veldhuisen Dirk J, Völker Uwe, Whitfield John B, Willemsen Gonneke, Winkelmann Bernhard R, Wirnsberger Gerald, Algra Ale, Cucca Francesco, d'Adamo Adamo Pio, Danesh John, Deary Ian J, Dominiczak Anna F, Elliott Paul, Fortina Paolo, Froguel Philippe, Gasparini Paolo, Greinacher Andreas, Hazen Stanley L, Jarvelin Marjo-Riitta, Tee Khaw Kay, Lehtimäki Terho, Maerz Winfried, Martin Nicholas G, Metspalu Andres, Mitchell Braxton D, Montgomery Grant W, Moore Carmel, Navis Gerjan, Pirastu Mario, Pramstaller Peter P, Ramirez-Solis Ramiro, Schadt Eric, Scott James, Shuldiner Alan R, Davey Smith George, Gustav Smith J, Snieder Harold, Sorice Rossella, Spector Tim D, Stefansson Kari, Stumvoll Michael, Wilson Tang W H, Toniolo Daniela, Tönjes Anke, Visscher Peter M, Vollenweider Peter, Wareham Nicholas J, Wolffenbuttel Bruce H R, Boomsma Dorret I, Beckmann Jacques S, Dedoussis George V, Deloukas Panos, Ferreira Manuel A, Sanna Serena, Uda Manuela, Hicks Andrew A, Martin Penninger Josef, Gieger Christian, Kooner Jaspal S, Ouwehand Willem H, Soranzo Nicole, Chambers John C in Nature (2012). PubMed

Abstract

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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