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

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.T.; 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.J.; Kanoni, S.; Kleber, M.E.; Lagou, V.; Langenberg, C.; Lopez, L.M.; Lyytikäinen, L.P.; 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.Y.; Tang, C.S.; Teumer, A.; Traglia, M.; Ulivi, S.; Westra, H.J.; Yang, J.; Zhao, J.H.; 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.; de Boer, R.A.; de Geus, E.J.; de Moor, M.H.; Dimitriou, M.; Domingues, F.S.; Döring, A.; Engström, G.; Eyjolfsson, G.I.; Ferrucci, L.; Fischer, K.; Galanello, R.; Garner, S.F.; Genser, B.; Gibson, Q.D.; Girotto, G.; Gudbjartsson, D.F.; Harris, S.E.; Hartikainen, A.L.; 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.; 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.; Schmidt, C.O.; Silljé, H.H.; Sladek, R.; Smit, J.H.; Starr, J.M.; Stephens, J.; Sulem, P.; Tanaka, T.; Thorsteinsdottir, U.; Tragante, V.; van Gilst, W.H.; van Pelt, L.J.; 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.R.; Khaw, K.T.; 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.; Smith, G.D.; Smith, J.G.; Snieder, H.; Sorice, R.; Spector, T.D.; Stefansson, K.; Stumvoll, M.; Tang, W.H.; Toniolo, D.; Tönjes, A.; Visscher, P.M.; Vollenweider, P.; Wareham, N.J.; Wolffenbuttel, B.H.; Boomsma, D.I.; Beckmann, J.S.; Dedoussis, G.V.; Deloukas, P.; Ferreira, M.A.; Sanna, S.; Uda, M.; Hicks, A.A.; Penninger, J.M.; Gieger, C.; Kooner, J.S.; Ouwehand, W.H.; Soranzo, N.; Chambers, J.C.

doi:10.1038/nature11677

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

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Download: BIB_A33D6D054D38.P001.pdf (2112.71 [Ko])
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Serval ID

serval:BIB_A33D6D054D38

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

Nature

Author(s)

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.T., 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.J., Kanoni S., Kleber M.E., Lagou V., Langenberg C., Lopez L.M., Lyytikäinen L.P., 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.Y., Tang C.S., Teumer A., Traglia M., Ulivi S., Westra H.J., Yang J., Zhao J.H., 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., de Boer R.A., de Geus E.J., de Moor M.H., Dimitriou M., Domingues F.S., Döring A., Engström G., Eyjolfsson G.I., Ferrucci L., Fischer K., Galanello R., Garner S.F., Genser B., Gibson Q.D., Girotto G., Gudbjartsson D.F., Harris S.E., Hartikainen A.L., 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., 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., Schmidt C.O., Silljé H.H., Sladek R., Smit J.H., Starr J.M., Stephens J., Sulem P., Tanaka T., Thorsteinsdottir U., Tragante V., van Gilst W.H., van Pelt L.J., 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.R., Khaw K.T., 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., Smith G.D., Smith J.G., Snieder H., Sorice R., Spector T.D., Stefansson K., Stumvoll M., Tang W.H., Toniolo D., Tönjes A., Visscher P.M., Vollenweider P., Wareham N.J., Wolffenbuttel B.H., Boomsma D.I., Beckmann J.S., Dedoussis G.V., Deloukas P., Ferreira M.A., Sanna S., Uda M., Hicks A.A., Penninger J.M., Gieger C., Kooner J.S., Ouwehand W.H., Soranzo N., Chambers J.C.

ISSN

1476-4687 (Electronic)

ISSN-L

0028-0836

Publication state

Published

Issued date

2012

Peer-reviewed

Oui

Volume

492

Number

7429

Pages

369-375

Language

english

Notes

Publication types: Journal Article Publication Status: ppublish PDF type: Article

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.

URN

urn:nbn:ch:serval-BIB_A33D6D054D386

OAI-PMH

oai:serval.unil.ch:BIB_A33D6D054D38

DOI

10.1038/nature11677

Pubmed

23222517

Web of science

000312488200044

Open Access

Yes