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Seventy-five genetic loci influencing the human red blood cell

van der Harst, Pim; Zhang, Weihua; Leach, Irene Mateo; Rendon, Augusto; Verweij, Niek; Sehmi, Joban; Paul, Dirk S.; Elling, Ulrich; Allayee, Hooman and Li, Xinzhong, et al. (2012) In Nature 492(7429). p.369-375
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... (More)
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. (Less)
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Nature
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492
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7429
pages
369 - 375
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Nature Publishing Group
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  • scopus:84871464519
ISSN
0028-0836
DOI
10.1038/nature11677
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English
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06878129-f8e8-467a-9157-70455386518a (old id 3366396)
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@article{06878129-f8e8-467a-9157-70455386518a,
  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 &lt; 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 Zhang, Weihua and Leach, Irene Mateo and Rendon, Augusto and Verweij, Niek and Sehmi, Joban and Paul, Dirk S. and Elling, Ulrich and Allayee, Hooman and Li, Xinzhong and Radhakrishnan, Aparna and Tan, Sian-Tsung and Voss, Katrin and Weichenberger, Christian X. and Albers, Cornelis A. and Al-Hussani, Abtehale and Asselbergs, Folkert W. and Ciullo, Marina and Danjou, Fabrice and Dina, Christian and Esko, Tonu and Evans, David M. and Franke, Lude and Goegele, Martin and Hartiala, Jaana and Hersch, Micha and Holm, Hilma and Hottenga, Jouke-Jan and Kanoni, Stavroula and Kleber, Marcus E. and Lagou, Vasiliki and Langenberg, Claudia and Lopez, Lorna M. and Lyytikainen, Leo-Pekka and Melander, Olle and Murgia, Federico and Nolte, Ilja M. and O'Reilly, Paul F. and Padmanabhan, Sandosh and Parsa, Afshin and Pirastu, Nicola and Porcu, Eleonora and Portas, Laura and Prokopenko, Inga and Ried, Janina S. and Shin, So-Youn and Tang, Clara S. and Teumer, Alexander and Traglia, Michela and Ulivi, Sheila and Westra, Harm-Jan and Yang, Jian and Zhao, Jing Hua and Anni, Franco and Abdellaoui, Abdel and Attwood, Antony and Balkau, Beverley and Bandinelli, Stefania and Bastardot, Francois and Benyamin, Beben and Boehm, Bernhard O. and Cookson, William O. and Das, Debashish and de Bakker, Paul I. W. and de Boer, Rudolf A. and de Geus, Eco J. C. and de Moor, Marleen H. and Dimitriou, Maria and Domingues, Francisco S. and Doering, Angela and Engström, Gunnar and Eyjolfsson, Gudmundur Ingi and Ferrucci, Luigi and Fischer, Krista and Galanello, Renzo and Garner, Stephen F. and Genser, Bernd and Gibson, Quince D. and Girotto, Giorgia and Gudbjartsson, Daniel Fannar and Harris, Sarah E. and Hartikainen, Anna-Liisa and Hastie, Claire E. and Hedblad, Bo and Illig, Thomas and Jolley, Jennifer and Kahonen, Mika and Kema, Ido P. and Kemp, John P. and Liang, Liming and Lloyd-Jones, Heather and Loos, Ruth J. F. and Meacham, Stuart and Medland, Sarah E. and Meisinger, Christa and Memari, Yasin and Mihailov, Evelin and Miller, Kathy and Moffatt, Miriam F. and Nauck, Matthias and Novatchkova, Maria and Nutile, Teresa and Olafsson, Isleifur and Onundarson, Pall T. and Parracciani, Debora and Penninx, Brenda W. and Perseu, Lucia and Piga, Antonio and Pistis, Giorgio and Pouta, Anneli and Puc, Ursula and Raitakari, Olli and Ring, Susan M. and Robino, Antonietta and Ruggiero, Daniela and Ruokonen, Aimo and Saint-Pierre, Aude and Sala, Cinzia and Salumets, Andres and Sambrook, Jennifer and Schepers, Hein and Schmidt, Carsten Oliver and Sillje, Herman H. W. and Sladek, Rob and Smit, Johannes H. and Starr, John M. and Stephens, Jonathan and Sulem, Patrick and Tanaka, Toshiko and Thorsteinsdottir, Unnur and Tragante, Vinicius and van Gilst, Wiek H. and van Pelt, L. Joost and van Veldhuisen, Dirk J. and Voelker, Uwe and Whitfield, John B. and Willemsen, Gonneke and Winkelmann, Bernhard R. and Wirnsberger, Gerald and Algra, Ale and Cucca, Francesco and d'Adamo, Adamo Pio and Danesh, John and Deary, Ian J. and Dominiczak, Anna F. and Elliott, Paul and Fortina, Paolo and Froguel, Philippe and Gasparini, Paolo and Greinacher, Andreas and Hazen, Stanley L. and Jarvelin, Marjo-Riitta and Khaw, Kay Tee and Lehtimaki, Terho and Maerz, Winfried and Martin, Nicholas G. and Metspalu, Andres and Mitchell, Braxton D. and Montgomery, Grant W. and Moore, Carmel and Navis, Gerjan and Pirastu, Mario and Pramstaller, Peter P. and Ramirez-Solis, Ramiro and Schadt, Eric and Scott, James and Shuldiner, Alan R. and Smith, George Davey and Smith, Gustav and Snieder, Harold and Sorice, Rossella and Spector, Tim D. and Stefansson, Kari and Stumvoll, Michael and Tang, W. H. Wilson and Toniolo, Daniela and Toenjes, Anke and Visscher, Peter M. and Vollenweider, Peter and Wareham, Nicholas J. and Wolffenbuttel, Bruce H. R. and Boomsma, Dorret I. and Beckmann, Jacques S. and Dedoussis, George V. and Deloukas, Panos and Ferreira, Manuel A. and Sanna, Serena and Uda, Manuela and Hicks, Andrew A. and Penninger, Josef Martin and Gieger, Christian and Kooner, Jaspal S. and Ouwehand, Willem H. and Soranzo, Nicole and Chambers, John C.},
  issn         = {0028-0836},
  language     = {eng},
  number       = {7429},
  pages        = {369--375},
  publisher    = {Nature Publishing Group},
  series       = {Nature},
  title        = {Seventy-five genetic loci influencing the human red blood cell},
  url          = {http://dx.doi.org/10.1038/nature11677},
  volume       = {492},
  year         = {2012},
}