Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium

Santhi K. Ganesh; Neil A. Zakai; Frank J.A. Van Rooij; Nicole Soranzo; Albert V. Smith; Michael A. Nalls; Ming Huei Chen; Anna Kottgen; Nicole L. Glazer; Abbas Dehghan; Brigitte Kuhnel; Thor Aspelund; Qiong Yang; Toshiko Tanaka; Andrew Jaffe; Joshua C.M. Bis; Germaine C. Verwoert; Alexander Teumer; Caroline S. Fox; Jack M. Guralnik; Georg B. Ehret; Kenneth Rice; Janine F. Felix; Augusto Rendon; Gudny Eiriksdottir; Daniel Levy; Kushang V. Patel; Eric Boerwinkle; Jerome I. Rotter; Albert Hofman; Jennifer G. Sambrook; Dena G. Hernandez; Gang Zheng; Stefania Bandinelli; Andrew B. Singleton; Josef Coresh; Thomas Lumley; André G. Uitterlinden; Janine M. Vangils; Lenore J. Launer; L. Adrienne Cupples; Ben A. Oostra; Jaap Jan Zwaginga; Willem H. Ouwehand; Swee Lay Thein; Christa Meisinger; Panos Deloukas; Matthias Nauck; Tim D. Spector; Christian Gieger; Vilmundur Gudnason; Cornelia M. Van Duijn; Bruce M. Psaty; Luigi Ferrucci; Aravinda Chakravarti; Andreas Greinacher; Christopher J. O'Donnell; Jacqueline C.M. Witteman; Susan Furth; Mary Cushman; Tamara B. Harris; Jing Ping Lin

doi:10.1038/ng.466

Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium

Santhi K. Ganesh, Neil A. Zakai, Frank J.A. Van Rooij, Nicole Soranzo, Albert V. Smith, Michael A. Nalls, Ming Huei Chen, Anna Kottgen, Nicole L. Glazer, Abbas Dehghan, Brigitte Kuhnel, Thor Aspelund, Qiong Yang, Toshiko Tanaka, Andrew Jaffe, Joshua C.M. Bis, Germaine C. Verwoert, Alexander Teumer, Caroline S. Fox, Jack M. GuralnikGeorg B. Ehret, Kenneth Rice, Janine F. Felix, Augusto Rendon, Gudny Eiriksdottir, Daniel Levy, Kushang V. Patel, Eric Boerwinkle, Jerome I. Rotter, Albert Hofman, Jennifer G. Sambrook, Dena G. Hernandez, Gang Zheng, Stefania Bandinelli, Andrew B. Singleton, Josef Coresh, Thomas Lumley, André G. Uitterlinden, Janine M. Vangils, Lenore J. Launer, L. Adrienne Cupples, Ben A. Oostra, Jaap Jan Zwaginga, Willem H. Ouwehand, Swee Lay Thein, Christa Meisinger, Panos Deloukas, Matthias Nauck, Tim D. Spector, Christian Gieger, Vilmundur Gudnason, Cornelia M. Van Duijn, Bruce M. Psaty, Luigi Ferrucci, Aravinda Chakravarti, Andreas Greinacher, Christopher J. O'Donnell, Jacqueline C.M. Witteman, Susan Furth, Mary Cushman, Tamara B. Harris, Jing Ping Lin

Bloomberg School of Public Health

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

263 Scopus citations

Abstract

Measurements of erythrocytes within the blood are important clinical traits and can indicate various hematological disorders. We report here genome-wide association studies (GWAS) for six erythrocyte traits, including hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red blood cell count (RBC). We performed an initial GWAS in cohorts of the CHARGE Consortium totaling 24,167 individuals of European ancestry and replication in additional independent cohorts of the HaemGen Consortium totaling 9,456 individuals. We identified 23 loci significantly associated with these traits in a meta-analysis of the discovery and replication cohorts (combined P values ranging from 5 × 10 8 to 7 × 10 86). Our findings include loci previously associated with these traits (HBS1L-MYB, HFE, TMPRSS6, TFR2, SPTA1) as well as new associations (EPO, TFRC, SH2B3 and 15 other loci). This study has identified new determinants of erythrocyte traits, offering insight into common variants underlying variation in erythrocyte measures.

Original language	English (US)
Pages (from-to)	1191-1198
Number of pages	8
Journal	Nature genetics
Volume	41
Issue number	11
DOIs	https://doi.org/10.1038/ng.466
State	Published - Nov 2009

ASJC Scopus subject areas

Genetics

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Ganesh, S. K., Zakai, N. A., Van Rooij, F. J. A., Soranzo, N., Smith, A. V., Nalls, M. A., Chen, M. H., Kottgen, A., Glazer, N. L., Dehghan, A., Kuhnel, B., Aspelund, T., Yang, Q., Tanaka, T., Jaffe, A., Bis, J. C. M., Verwoert, G. C., Teumer, A., Fox, C. S., ... Lin, J. P. (2009). Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium. Nature genetics, 41(11), 1191-1198. https://doi.org/10.1038/ng.466

Ganesh, SK, Zakai, NA, Van Rooij, FJA, Soranzo, N, Smith, AV, Nalls, MA, Chen, MH, Kottgen, A, Glazer, NL, Dehghan, A, Kuhnel, B, Aspelund, T, Yang, Q, Tanaka, T, Jaffe, A, Bis, JCM, Verwoert, GC, Teumer, A, Fox, CS, Guralnik, JM, Ehret, GB, Rice, K, Felix, JF, Rendon, A, Eiriksdottir, G, Levy, D, Patel, KV, Boerwinkle, E, Rotter, JI, Hofman, A, Sambrook, JG, Hernandez, DG, Zheng, G, Bandinelli, S, Singleton, AB, Coresh, J, Lumley, T, Uitterlinden, AG, Vangils, JM, Launer, LJ, Cupples, LA, Oostra, BA, Zwaginga, JJ, Ouwehand, WH, Thein, SL, Meisinger, C, Deloukas, P, Nauck, M, Spector, TD, Gieger, C, Gudnason, V, Van Duijn, CM, Psaty, BM, Ferrucci, L, Chakravarti, A, Greinacher, A, O'Donnell, CJ, Witteman, JCM, Furth, S, Cushman, M, Harris, TB & Lin, JP 2009, 'Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium', Nature genetics, vol. 41, no. 11, pp. 1191-1198. https://doi.org/10.1038/ng.466

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title = "Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium",

abstract = "Measurements of erythrocytes within the blood are important clinical traits and can indicate various hematological disorders. We report here genome-wide association studies (GWAS) for six erythrocyte traits, including hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red blood cell count (RBC). We performed an initial GWAS in cohorts of the CHARGE Consortium totaling 24,167 individuals of European ancestry and replication in additional independent cohorts of the HaemGen Consortium totaling 9,456 individuals. We identified 23 loci significantly associated with these traits in a meta-analysis of the discovery and replication cohorts (combined P values ranging from 5 × 10 8 to 7 × 10 86). Our findings include loci previously associated with these traits (HBS1L-MYB, HFE, TMPRSS6, TFR2, SPTA1) as well as new associations (EPO, TFRC, SH2B3 and 15 other loci). This study has identified new determinants of erythrocyte traits, offering insight into common variants underlying variation in erythrocyte measures.",

author = "Ganesh, {Santhi K.} and Zakai, {Neil A.} and {Van Rooij}, {Frank J.A.} and Nicole Soranzo and Smith, {Albert V.} and Nalls, {Michael A.} and Chen, {Ming Huei} and Anna Kottgen and Glazer, {Nicole L.} and Abbas Dehghan and Brigitte Kuhnel and Thor Aspelund and Qiong Yang and Toshiko Tanaka and Andrew Jaffe and Bis, {Joshua C.M.} and Verwoert, {Germaine C.} and Alexander Teumer and Fox, {Caroline S.} and Guralnik, {Jack M.} and Ehret, {Georg B.} and Kenneth Rice and Felix, {Janine F.} and Augusto Rendon and Gudny Eiriksdottir and Daniel Levy and Patel, {Kushang V.} and Eric Boerwinkle and Rotter, {Jerome I.} and Albert Hofman and Sambrook, {Jennifer G.} and Hernandez, {Dena G.} and Gang Zheng and Stefania Bandinelli and Singleton, {Andrew B.} and Josef Coresh and Thomas Lumley and Uitterlinden, {Andr{\'e} G.} and Vangils, {Janine M.} and Launer, {Lenore J.} and Cupples, {L. Adrienne} and Oostra, {Ben A.} and Zwaginga, {Jaap Jan} and Ouwehand, {Willem H.} and Thein, {Swee Lay} and Christa Meisinger and Panos Deloukas and Matthias Nauck and Spector, {Tim D.} and Christian Gieger and Vilmundur Gudnason and {Van Duijn}, {Cornelia M.} and Psaty, {Bruce M.} and Luigi Ferrucci and Aravinda Chakravarti and Andreas Greinacher and O'Donnell, {Christopher J.} and Witteman, {Jacqueline C.M.} and Susan Furth and Mary Cushman and Harris, {Tamara B.} and Lin, {Jing Ping}",

year = "2009",

month = nov,

doi = "10.1038/ng.466",

language = "English (US)",

volume = "41",

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T1 - Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium

AU - Ganesh, Santhi K.

AU - Zakai, Neil A.

AU - Van Rooij, Frank J.A.

AU - Soranzo, Nicole

AU - Smith, Albert V.

AU - Nalls, Michael A.

AU - Chen, Ming Huei

AU - Kottgen, Anna

AU - Glazer, Nicole L.

AU - Dehghan, Abbas

AU - Kuhnel, Brigitte

AU - Aspelund, Thor

AU - Yang, Qiong

AU - Tanaka, Toshiko

AU - Jaffe, Andrew

AU - Bis, Joshua C.M.

AU - Verwoert, Germaine C.

AU - Teumer, Alexander

AU - Fox, Caroline S.

AU - Guralnik, Jack M.

AU - Ehret, Georg B.

AU - Rice, Kenneth

AU - Felix, Janine F.

AU - Rendon, Augusto

AU - Eiriksdottir, Gudny

AU - Levy, Daniel

AU - Patel, Kushang V.

AU - Boerwinkle, Eric

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AU - Hernandez, Dena G.

AU - Zheng, Gang

AU - Bandinelli, Stefania

AU - Singleton, Andrew B.

AU - Coresh, Josef

AU - Lumley, Thomas

AU - Uitterlinden, André G.

AU - Vangils, Janine M.

AU - Launer, Lenore J.

AU - Cupples, L. Adrienne

AU - Oostra, Ben A.

AU - Zwaginga, Jaap Jan

AU - Ouwehand, Willem H.

AU - Thein, Swee Lay

AU - Meisinger, Christa

AU - Deloukas, Panos

AU - Nauck, Matthias

AU - Spector, Tim D.

AU - Gieger, Christian

AU - Gudnason, Vilmundur

AU - Van Duijn, Cornelia M.

AU - Psaty, Bruce M.

AU - Ferrucci, Luigi

AU - Chakravarti, Aravinda

AU - Greinacher, Andreas

AU - O'Donnell, Christopher J.

AU - Witteman, Jacqueline C.M.

AU - Furth, Susan

AU - Cushman, Mary

AU - Harris, Tamara B.

AU - Lin, Jing Ping

PY - 2009/11

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N2 - Measurements of erythrocytes within the blood are important clinical traits and can indicate various hematological disorders. We report here genome-wide association studies (GWAS) for six erythrocyte traits, including hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red blood cell count (RBC). We performed an initial GWAS in cohorts of the CHARGE Consortium totaling 24,167 individuals of European ancestry and replication in additional independent cohorts of the HaemGen Consortium totaling 9,456 individuals. We identified 23 loci significantly associated with these traits in a meta-analysis of the discovery and replication cohorts (combined P values ranging from 5 × 10 8 to 7 × 10 86). Our findings include loci previously associated with these traits (HBS1L-MYB, HFE, TMPRSS6, TFR2, SPTA1) as well as new associations (EPO, TFRC, SH2B3 and 15 other loci). This study has identified new determinants of erythrocyte traits, offering insight into common variants underlying variation in erythrocyte measures.

AB - Measurements of erythrocytes within the blood are important clinical traits and can indicate various hematological disorders. We report here genome-wide association studies (GWAS) for six erythrocyte traits, including hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red blood cell count (RBC). We performed an initial GWAS in cohorts of the CHARGE Consortium totaling 24,167 individuals of European ancestry and replication in additional independent cohorts of the HaemGen Consortium totaling 9,456 individuals. We identified 23 loci significantly associated with these traits in a meta-analysis of the discovery and replication cohorts (combined P values ranging from 5 × 10 8 to 7 × 10 86). Our findings include loci previously associated with these traits (HBS1L-MYB, HFE, TMPRSS6, TFR2, SPTA1) as well as new associations (EPO, TFRC, SH2B3 and 15 other loci). This study has identified new determinants of erythrocyte traits, offering insight into common variants underlying variation in erythrocyte measures.

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JO - Nature genetics

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Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium

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