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.

Détails

Télécharger: BIB_A33D6D054D38.P001.pdf (2112.71 [Ko])
Etat: Public
Version: de l'auteur⸱e

ID Serval

serval:BIB_A33D6D054D38

Type

Article: article d'un périodique ou d'un magazine.

Collection

Publications

Institution

UNIL/CHUV

Titre

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

Périodique

Nature

Auteur⸱e⸱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

Statut éditorial

Publié

Date de publication

2012

Peer-reviewed

Oui

Volume

492

Numéro

7429

Pages

369-375

Langue

anglais

Notes

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

Résumé

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

Oui