Seventy-five genetic loci influencing the human red blood cell

van der Harst, P. et al. (2012) Seventy-five genetic loci influencing the human red blood cell. Nature, 492(7429), pp. 369-375. (doi: 10.1038/nature11677) (PMID:23222517) (PMCID:PMC3623669)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Hastie, Dr Claire and Padmanabhan, Professor Sandosh and Dominiczak, Professor Anna
Authors: van der Harst, P., Zhang, W., Mateo Leach, I., Rendon, A., Verweij, N., Sehmi, J., Paul, D.S., Elling, U., Allayee, H., Li, X., Radhakrishnan, A., Tan, S., Voss, K., Weichenberger, C.X., Albers, C.A., Al-Hussani, A., Asselbergs, F.W., Ciullo, M., Danjou, F., Dina, C., Esko, T., Evans, D.M., Franke, L., Gögele, M., Hartiala, J., Hersch, M., Holm, H., Hottenga, J., Kanoni, S., Kleber, M.E., Lagou, V., Langenberg, C., Lopez, L.M., Lyytikäinen, L., Melander, O., Murgia, F., Nolte, I.M., O’Reilly, P.F., Padmanabhan, S., Parsa, A., Pirastu, N., Porcu, E., Portas, L., Prokopenko, I., Ried, J.S., Shin, S., Tang, C.S., Teumer, A., Traglia, M., Ulivi, S., Westra, H., Yang, J., Hua Zhao, J., Anni, F., Abdellaoui, A., Attwood, A., Balkau, B., Bandinelli, S., Bastardot, F., Benyamin, B., Boehm, B.O., Cookson, W.O., Das, D., de Bakker, P.I.W., de Boer, R.A., de Geus, E.J.C., de Moor, M.H., Dimitriou, M., Domingues, F.S., Döring, A., Engström, G., Ingi Eyjolfsson, G., Ferrucci, L., Fischer, K., Galanello, R., Garner, S.F., Genser, B., Gibson, Q.D., Girotto, G., Fannar Gudbjartsson, D., Harris, S.E., Hartikainen, A., Hastie, C.E., Hedblad, B., Illig, T., Jolley, J., Kähönen, M., Kema, I.P., Kemp, J.P., Liang, L., Lloyd-Jones, H., Loos, R.J.F., Meacham, S., Medland, S.E., Meisinger, C., Memari, Y., Mihailov, E., Miller, K., Moffatt, M.F., Nauck, M., Novatchkova, M., Nutile, T., Olafsson, I., Onundarson, P.T., Parracciani, D., Penninx, B.W., Perseu, L., Piga, A., Pistis, G., Pouta, A., Puc, U., Raitakari, O., Ring, S.M., Robino, A., Ruggiero, D., Ruokonen, A., Saint-Pierre, A., Sala, C., Salumets, A., Sambrook, J., Schepers, H., Oliver Schmidt, C., Silljé, H.H.W., Sladek, R., Smit, J.H., Starr, J.M., Stephens, J., Sulem, P., Tanaka, T., Thorsteinsdottir, U., Tragante, V., van Gilst, W.H., Joost van Pelt, L., van Veldhuisen, D.J., Völker, U., Whitfield, J.B., Willemsen, G., Winkelmann, B.R., Wirnsberger, G., Algra, A., Cucca, F., d’Adamo, A.P., Danesh, J., Deary, I.J., Dominiczak, A.F., Elliott, P., Fortina, P., Froguel, P., Gasparini, P., Greinacher, A., Hazen, S.L., Jarvelin, M., Tee Khaw, K., Lehtimäki, T., Maerz, W., Martin, N.G., Metspalu, A., Mitchell, B.D., Montgomery, G.W., Moore, C., Navis, G., Pirastu, M., Pramstaller, P.P., Ramirez-Solis, R., Schadt, E., Scott, J., Shuldiner, A.R., Davey Smith, G., Gustav Smith, J., Snieder, H., Sorice, R., Spector, T.D., Stefansson, K., Stumvoll, M., Wilson Tang, W.H., Toniolo, D., Tönjes, A., Visscher, P.M., Vollenweider, P., Wareham, N.J., Wolffenbuttel, B.H.R., Boomsma, D.I., Beckmann, J.S., Dedoussis, G.V., Deloukas, P., Ferreira, M.A., Sanna, S., Uda, M., Hicks, A.A., Martin Penninger, J., Gieger, C., Kooner, J.S., Ouwehand, W.H., Soranzo, N., and Chambers, J.C.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Nature
Publisher:Nature Publishing Group
ISSN (Online):1476-4687
Published Online:05 December 2012
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