Seventy-five genetic loci influencing the human red blood cell

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

doi:https://doi.org/10.1038/nature11677

Seventy-five genetic loci influencing the human red blood cell

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

Psychiatry (VUmc)

Research output: Contribution to journal › Article › Academic › peer-review

247 Citations (Scopus)

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. © 2012 Macmillan Publishers Limited. All rights reserved.

Original language	English
Pages (from-to)	369-375
Journal	NATURE
Volume	492
Issue number	7429
DOIs	https://doi.org/10.1038/nature11677
Publication status	Published - 20 Dec 2012

Cohort Studies

Netherlands Twin Register (NTR)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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https://doi.org/10.1038/nature11677

Cite this

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., ... Pisits, G. (2012). Seventy-five genetic loci influencing the human red blood cell. NATURE, 492(7429), 369-375. https://doi.org/10.1038/nature11677

@article{14df4aff1b2046f58ea6e40c11eba083,

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. {\textcopyright} 2012 Macmillan Publishers Limited. All rights reserved.",

author = "{van der Harst}, Pim and Weihua Zhang and {Mateo Leach}, Irene 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 Esko, {T. nu} and Evans, {David M.} and Lude Franke and Martin G{\"o}gele 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 Lyytik{\"a}inen 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 {Hua Zhao}, Jing and Franco Anni and Abdel Abdellaoui and Antony Attwood and Beverley Balkau and Stefania Bandinelli and Fran{\c c}ois 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 D{\"o}ring 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 K{\"a}h{\"o}nen 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 Sillj{\'e}, {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 {Joost van Pelt}, L. and {van Veldhuisen}, {Dirk J.} and Uwe V{\"o}lker 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 Lehtim{\"a}ki 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}, J. and Harold Snieder and Rossella Sorice and Spector, {Tim D.} and Kari Stefansson and Michael Stumvoll and {Wilson Tang}, {W. H.} and Daniela Toniolo and Anke T{\"o}njes 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.} and G. Pisits",

year = "2012",

month = dec,

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doi = "https://doi.org/10.1038/nature11677",

language = "English",

volume = "492",

pages = "369--375",

journal = "NATURE",

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publisher = "Nature Publishing Group",

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van der Harst, P, Zhang, W, Mateo Leach, I, Rendon, A, Verweij, N, Sehmi, J, Paul, DS, Elling, U, Allayee, H, Li, X, Radhakrishnan, A, Tan, S-T, Voss, K, Weichenberger, CX, Albers, CA, Al-Hussani, A, Asselbergs, FW, Ciullo, M, Danjou, F, Dina, C, Esko, TN, Evans, DM, Franke, L, Gögele, M, Hartiala, J, Hersch, M, Holm, H, Hottenga, J-J, Kanoni, S, Kleber, ME, Lagou, V, Langenberg, C, Lopez, LM, Lyytikäinen, L-P, Melander, O, Murgia, F, Nolte, IM, O'Reilly, PF, Padmanabhan, S, Parsa, A, Pirastu, N, Porcu, E, Portas, L, Prokopenko, I, Ried, JS, Shin, S-Y, Tang, CS, Teumer, A, Traglia, M, Ulivi, S, Westra, H-J, Yang, J, Hua Zhao, J, Anni, F, Abdellaoui, A, Attwood, A, Balkau, B, Bandinelli, S, Bastardot, F, Benyamin, B, Boehm, BO, Cookson, WO, Das, D, de Bakker, PIW, de Boer, RA, de Geus, EJC, de Moor, MH, Dimitriou, M, Domingues, FS, Döring, A, Engström, G, Eyjolfsson, GI, Ferrucci, L, Fischer, K, Galanello, R, Garner, SF, Genser, B, Gibson, QD, Girotto, G, Gudbjartsson, DF, Harris, SE, Hartikainen, A-L, Hastie, CE, Hedblad, B, Illig, T, Jolley, J, Kähönen, M, Kema, IP, Kemp, JP, Liang, L, Lloyd-Jones, H, Loos, RJF, Meacham, S, Medland, SE, Meisinger, C, Memari, Y, Mihailov, E, Miller, K, Moffatt, MF, Nauck, M, Novatchkova, M, Nutile, T, Olafsson, I, Onundarson, PT, Parracciani, D, Penninx, BW, Perseu, L, Piga, A, Pistis, G, Pouta, A, Puc, U, Raitakari, O, Ring, SM, Robino, A, Ruggiero, D, Ruokonen, A, Saint-Pierre, A, Sala, C, Salumets, A, Sambrook, J, Schepers, H, Schmidt, CO, Silljé, HHW, Sladek, R, Smit, JH, Starr, JM, Stephens, J, Sulem, P, Tanaka, T, Thorsteinsdottir, U, Tragante, V, van Gilst, WH, Joost van Pelt, L, van Veldhuisen, DJ, Völker, U, Whitfield, JB, Willemsen, G, Winkelmann, BR, Wirnsberger, G, Algra, A, Cucca, F, D'Adamo, AP, Danesh, J, Deary, IJ, Dominiczak, AF, Elliott, P, Fortina, P, Froguel, P, Gasparini, P, Greinacher, A, Hazen, SL, Jarvelin, M-R, Khaw, KT, Lehtimäki, T, Maerz, W, Martin, NG, Metspalu, A, Mitchell, BD, Montgomery, GW, Moore, C, Navis, G, Pirastu, M, Pramstaller, PP, Ramirez-Solis, R, Schadt, E, Scott, J, Shuldiner, AR, Smith, GD, Gustav Smith, J, Snieder, H, Sorice, R, Spector, TD, Stefansson, K, Stumvoll, M, Wilson Tang, WH, Toniolo, D, Tönjes, A, Visscher, PM, Vollenweider, P, Wareham, NJ, Wolffenbuttel, BHR, Boomsma, DI, Beckmann, JS, Dedoussis, GV, Deloukas, P, Ferreira, MA, Sanna, S, Uda, M, Hicks, AA, Penninger, JM, Gieger, C, Kooner, JS, Ouwehand, WH, Soranzo, N, Chambers, JC & Pisits, G 2012, 'Seventy-five genetic loci influencing the human red blood cell', NATURE, vol. 492, no. 7429, pp. 369-375. https://doi.org/10.1038/nature11677

TY - JOUR

T1 - Seventy-five genetic loci influencing the human red blood cell

AU - van der Harst, Pim

AU - Zhang, Weihua

AU - Mateo Leach, Irene

AU - Rendon, Augusto

AU - Verweij, Niek

AU - Sehmi, Joban

AU - Paul, Dirk S.

AU - Elling, Ulrich

AU - Allayee, Hooman

AU - Li, Xinzhong

AU - Radhakrishnan, Aparna

AU - Tan, Sian-Tsung

AU - Voss, Katrin

AU - Weichenberger, Christian X.

AU - Albers, Cornelis A.

AU - Al-Hussani, Abtehale

AU - Asselbergs, Folkert W.

AU - Ciullo, Marina

AU - Danjou, Fabrice

AU - Dina, Christian

AU - Esko, T. nu

AU - Evans, David M.

AU - Franke, Lude

AU - Gögele, Martin

AU - Hartiala, Jaana

AU - Hersch, Micha

AU - Holm, Hilma

AU - Hottenga, Jouke-Jan

AU - Kanoni, Stavroula

AU - Kleber, Marcus E.

AU - Lagou, Vasiliki

AU - Langenberg, Claudia

AU - Lopez, Lorna M.

AU - Lyytikäinen, Leo-Pekka

AU - Melander, Olle

AU - Murgia, Federico

AU - Nolte, Ilja M.

AU - O'Reilly, Paul F.

AU - Padmanabhan, Sandosh

AU - Parsa, Afshin

AU - Pirastu, Nicola

AU - Porcu, Eleonora

AU - Portas, Laura

AU - Prokopenko, Inga

AU - Ried, Janina S.

AU - Shin, So-Youn

AU - Tang, Clara S.

AU - Teumer, Alexander

AU - Traglia, Michela

AU - Ulivi, Sheila

AU - Westra, Harm-Jan

AU - Yang, Jian

AU - Hua Zhao, Jing

AU - Anni, Franco

AU - Abdellaoui, Abdel

AU - Attwood, Antony

AU - Balkau, Beverley

AU - Bandinelli, Stefania

AU - Bastardot, François

AU - Benyamin, Beben

AU - Boehm, Bernhard O.

AU - Cookson, William O.

AU - Das, Debashish

AU - de Bakker, Paul I. W.

AU - de Boer, Rudolf A.

AU - de Geus, Eco J. C.

AU - de Moor, Marleen H.

AU - Dimitriou, Maria

AU - Domingues, Francisco S.

AU - Döring, Angela

AU - Engström, Gunnar

AU - Eyjolfsson, Gudmundur Ingi

AU - Ferrucci, Luigi

AU - Fischer, Krista

AU - Galanello, Renzo

AU - Garner, Stephen F.

AU - Genser, Bernd

AU - Gibson, Quince D.

AU - Girotto, Giorgia

AU - Gudbjartsson, Daniel Fannar

AU - Harris, Sarah E.

AU - Hartikainen, Anna-Liisa

AU - Hastie, Claire E.

AU - Hedblad, Bo

AU - Illig, Thomas

AU - Jolley, Jennifer

AU - Kähönen, Mika

AU - Kema, Ido P.

AU - Kemp, John P.

AU - Liang, Liming

AU - Lloyd-Jones, Heather

AU - Loos, Ruth J. F.

AU - Meacham, Stuart

AU - Medland, Sarah E.

AU - Meisinger, Christa

AU - Memari, Yasin

AU - Mihailov, Evelin

AU - Miller, Kathy

AU - Moffatt, Miriam F.

AU - Nauck, Matthias

AU - Novatchkova, Maria

AU - Nutile, Teresa

AU - Olafsson, Isleifur

AU - Onundarson, Pall T.

AU - Parracciani, Debora

AU - Penninx, Brenda W.

AU - Perseu, Lucia

AU - Piga, Antonio

AU - Pistis, Giorgio

AU - Pouta, Anneli

AU - Puc, Ursula

AU - Raitakari, Olli

AU - Ring, Susan M.

AU - Robino, Antonietta

AU - Ruggiero, Daniela

AU - Ruokonen, Aimo

AU - Saint-Pierre, Aude

AU - Sala, Cinzia

AU - Salumets, Andres

AU - Sambrook, Jennifer

AU - Schepers, Hein

AU - Schmidt, Carsten Oliver

AU - Silljé, Herman H. W.

AU - Sladek, Rob

AU - Smit, Johannes H.

AU - Starr, John M.

AU - Stephens, Jonathan

AU - Sulem, Patrick

AU - Tanaka, Toshiko

AU - Thorsteinsdottir, Unnur

AU - Tragante, Vinicius

AU - van Gilst, Wiek H.

AU - Joost van Pelt, L.

AU - van Veldhuisen, Dirk J.

AU - Völker, Uwe

AU - Whitfield, John B.

AU - Willemsen, Gonneke

AU - Winkelmann, Bernhard R.

AU - Wirnsberger, Gerald

AU - Algra, Ale

AU - Cucca, Francesco

AU - D'Adamo, Adamo Pio

AU - Danesh, John

AU - Deary, Ian J.

AU - Dominiczak, Anna F.

AU - Elliott, Paul

AU - Fortina, Paolo

AU - Froguel, Philippe

AU - Gasparini, Paolo

AU - Greinacher, Andreas

AU - Hazen, Stanley L.

AU - Jarvelin, Marjo-Riitta

AU - Khaw, Kay Tee

AU - Lehtimäki, Terho

AU - Maerz, Winfried

AU - Martin, Nicholas G.

AU - Metspalu, Andres

AU - Mitchell, Braxton D.

AU - Montgomery, Grant W.

AU - Moore, Carmel

AU - Navis, Gerjan

AU - Pirastu, Mario

AU - Pramstaller, Peter P.

AU - Ramirez-Solis, Ramiro

AU - Schadt, Eric

AU - Scott, James

AU - Shuldiner, Alan R.

AU - Smith, George Davey

AU - Gustav Smith, J.

AU - Snieder, Harold

AU - Sorice, Rossella

AU - Spector, Tim D.

AU - Stefansson, Kari

AU - Stumvoll, Michael

AU - Wilson Tang, W. H.

AU - Toniolo, Daniela

AU - Tönjes, Anke

AU - Visscher, Peter M.

AU - Vollenweider, Peter

AU - Wareham, Nicholas J.

AU - Wolffenbuttel, Bruce H. R.

AU - Boomsma, Dorret I.

AU - Beckmann, Jacques S.

AU - Dedoussis, George V.

AU - Deloukas, Panos

AU - Ferreira, Manuel A.

AU - Sanna, Serena

AU - Uda, Manuela

AU - Hicks, Andrew A.

AU - Penninger, Josef Martin

AU - Gieger, Christian

AU - Kooner, Jaspal S.

AU - Ouwehand, Willem H.

AU - Soranzo, Nicole

AU - Chambers, John C.

AU - Pisits, G.

PY - 2012/12/20

Y1 - 2012/12/20

N2 - 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. © 2012 Macmillan Publishers Limited. All rights reserved.

AB - 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. © 2012 Macmillan Publishers Limited. All rights reserved.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84871464519&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/23222517

U2 - https://doi.org/10.1038/nature11677

DO - https://doi.org/10.1038/nature11677

M3 - Article

C2 - 23222517

SN - 0028-0836

VL - 492

SP - 369

EP - 375

JO - NATURE

JF - NATURE

IS - 7429

ER -

Seventy-five genetic loci influencing the human red blood cell

Abstract

Cohort Studies

UN SDGs

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