Seventy-five genetic loci influencing the human red blood cell

Research output: Contribution to journalArticle


title = "Seventy-five genetic loci influencing the human red blood cell",
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.",
author = "{van der Harst}, Pim and Weihua Zhang and Leach, {Irene Mateo} and Augusto Rendon and Niek Verweij and Joban Sehmi and Paul, {Dirk S.} and Ulrich Elling and Hooman Allayee and Xinzhong Li and Aparna Radhakrishnan and Sian-Tsung Tan and Katrin Voss and Weichenberger, {Christian X.} and Albers, {Cornelis A.} and Abtehale Al-Hussani and Asselbergs, {Folkert W.} and Marina Ciullo and Fabrice Danjou and Christian Dina and Tonu Esko and Evans, {David M.} and Lude Franke and Martin Goegele and Jaana Hartiala and Micha Hersch and Hilma Holm and Jouke-Jan Hottenga and Stavroula Kanoni and Kleber, {Marcus E.} and Vasiliki Lagou and Claudia Langenberg and Lopez, {Lorna M.} and Leo-Pekka Lyytikainen and Olle Melander and Federico Murgia and Nolte, {Ilja M.} and O'Reilly, {Paul F.} and Sandosh Padmanabhan and Afshin Parsa and Nicola Pirastu and Eleonora Porcu and Laura Portas and Inga Prokopenko and Ried, {Janina S.} and So-Youn Shin and Tang, {Clara S.} and Alexander Teumer and Michela Traglia and Sheila Ulivi and Harm-Jan Westra and Jian Yang and Zhao, {Jing Hua} and Franco Anni and Abdel Abdellaoui and Antony Attwood and Beverley Balkau and Stefania Bandinelli and Francois Bastardot and Beben Benyamin and Boehm, {Bernhard O.} and Cookson, {William O.} and Debashish Das and {de Bakker}, {Paul I. W.} and {de Boer}, {Rudolf A.} and {de Geus}, {Eco J. C.} and {de Moor}, {Marleen H.} and Maria Dimitriou and Domingues, {Francisco S.} and Angela Doering and Gunnar Engstr{\"o}m and Eyjolfsson, {Gudmundur Ingi} and Luigi Ferrucci and Krista Fischer and Renzo Galanello and Garner, {Stephen F.} and Bernd Genser and Gibson, {Quince D.} and Giorgia Girotto and Gudbjartsson, {Daniel Fannar} and Harris, {Sarah E.} and Anna-Liisa Hartikainen and Hastie, {Claire E.} and Bo Hedblad and Thomas Illig and Jennifer Jolley and Mika Kahonen and Kema, {Ido P.} and Kemp, {John P.} and Liming Liang and Heather Lloyd-Jones and Loos, {Ruth J. F.} and Stuart Meacham and Medland, {Sarah E.} and Christa Meisinger and Yasin Memari and Evelin Mihailov and Kathy Miller and Moffatt, {Miriam F.} and Matthias Nauck and Maria Novatchkova and Teresa Nutile and Isleifur Olafsson and Onundarson, {Pall T.} and Debora Parracciani and Penninx, {Brenda W.} and Lucia Perseu and Antonio Piga and Giorgio Pistis and Anneli Pouta and Ursula Puc and Olli Raitakari and Ring, {Susan M.} and Antonietta Robino and Daniela Ruggiero and Aimo Ruokonen and Aude Saint-Pierre and Cinzia Sala and Andres Salumets and Jennifer Sambrook and Hein Schepers and Schmidt, {Carsten Oliver} and Sillje, {Herman H. W.} and Rob Sladek and Smit, {Johannes H.} and Starr, {John M.} and Jonathan Stephens and Patrick Sulem and Toshiko Tanaka and Unnur Thorsteinsdottir and Vinicius Tragante and {van Gilst}, {Wiek H.} and {van Pelt}, {L. Joost} and {van Veldhuisen}, {Dirk J.} and Uwe Voelker and Whitfield, {John B.} and Gonneke Willemsen and Winkelmann, {Bernhard R.} and Gerald Wirnsberger and Ale Algra and Francesco Cucca and d'Adamo, {Adamo Pio} and John Danesh and Deary, {Ian J.} and Dominiczak, {Anna F.} and Paul Elliott and Paolo Fortina and Philippe Froguel and Paolo Gasparini and Andreas Greinacher and Hazen, {Stanley L.} and Marjo-Riitta Jarvelin and Khaw, {Kay Tee} and Terho Lehtimaki and Winfried Maerz and Martin, {Nicholas G.} and Andres Metspalu and Mitchell, {Braxton D.} and Montgomery, {Grant W.} and Carmel Moore and Gerjan Navis and Mario Pirastu and Pramstaller, {Peter P.} and Ramiro Ramirez-Solis and Eric Schadt and James Scott and Shuldiner, {Alan R.} and Smith, {George Davey} and Gustav Smith and Harold Snieder and Rossella Sorice and Spector, {Tim D.} and Kari Stefansson and Michael Stumvoll and Tang, {W. H. Wilson} and Daniela Toniolo and Anke Toenjes and Visscher, {Peter M.} and Peter Vollenweider and Wareham, {Nicholas J.} and Wolffenbuttel, {Bruce H. R.} and Boomsma, {Dorret I.} and Beckmann, {Jacques S.} and Dedoussis, {George V.} and Panos Deloukas and Ferreira, {Manuel A.} and Serena Sanna and Manuela Uda and Hicks, {Andrew A.} and Penninger, {Josef Martin} and Christian Gieger and Kooner, {Jaspal S.} and Ouwehand, {Willem H.} and Nicole Soranzo and Chambers, {John C.}",
year = "2012",
doi = "10.1038/nature11677",
language = "English",
volume = "492",
pages = "369--375",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7429",