1. Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits
- Author
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Chami, N. (Nathalie), Chen, M.-H. (Ming-Huei), Slater, A.J. (Andrew J.), Eicher, J.D. (John D.), Evangelou, E. (Evangelos), Tajuddin, S.M. (Salman M.), Love-Gregory, L. (Latisha), Kacprowski, T. (Tim), Schick, U.M. (Ursula), Nomura, A. (Akihiro), Giri, A. (Ayush), Lessard, S. (Samuel), Brody, J.A. (Jennifer A.), Schurmann, C. (Claudia), Pankratz, V.S. (Shane), Yanek, L.R. (Lisa), Manichaikul, A. (Ani), Pazoki, R. (Raha), Mihailov, E. (Evelin), Hill, W.D. (W. David), Raffield, L.M. (Laura M.), Burt, A.D. (Alastair), Bartz, T.M. (Traci M.), Becker, D.M. (Diane), Becker, L.C. (Lewis), Boerwinkle, E.A. (Eric), Bork-Jensen, J. (Jette), Bottinger, E.P. (Erwin), O'Donoghue, M.L. (Michelle L.), Crosslin, D.R. (David), de Denus, S. (Simon), Dubé, M.-P. (Marie-Pierre), Elliott, P. (Paul), Engström, G., Evans, M.K. (Michele), Floyd, J. (James), Fornage, M. (Myriam), Gao, H. (He), Greinacher, A. (Andreas), Gudnason, V. (Vilmundur), Hansen, T. (T.), Harris, T.B. (Tamara), Hayward, C. (Caroline), Hernesniemi, J. (Jussi), Highland, H. (Heather), Hirschhorn, J.N. (Joel), Hofman, A. (Albert), Irvin, M.R. (Marguerite R.), Kähönen, M. (Mika), Lange, E.M. (Ethan), Launer, L.J. (Lenore J.), Lehtimäki, T. (Terho), Li, J. (Jin), Liewald, D.C.M. (David), Linneberg, A. (Allan), Liu, Y. (YongMei), Lu, Y. (Yingchang), Lyytikäinen, L.-P. (Leo-Pekka), Mägi, R. (Reedik), Mathias, J. (Jasmine), Melander, O. (Olle), Metspalu, A. (Andres), Mononen, K. (Kari), Nalls, M.A. (Michael), Nickerson, D.A. (Deborah), Nikus, K. (Kjell), O'Donnell, C.J. (Christopher), Orho-Melander, M. (Marju), Pedersen, O. (Oluf), Petersmann, A. (Astrid), Polfus, L. (Linda), Psaty, B.M. (Bruce), Raitakari, O.T. (Olli T.), Raitoharju, E. (Emma), Richard, M. (Melissa), Rice, K.M. (Kenneth), Rivadeneira Ramirez, F. (Fernando), Rotter, J.I. (Jerome I.), Schmidt, F. (Frank), Smith, A.V. (Albert Vernon), Starr, J.M. (John), Taylor, K.D. (Kent), Teumer, A. (Alexander), Thuesen, B.H. (Betina H.), Torstenson, E.S. (Eric S.), Tracy, R.P. (Russell), Tzoulaki, I., Zakai, N.A. (Neil), Vacchi-Suzzi, C. (Caterina), Duijn, C.M. (Cornelia) van, Rooij, F.J.A. (Frank) van, Cushman, M. (Mary Ann), Deary, I.J. (Ian), Velez Edwards, D.R. (Digna R.), Vergnaud, A.-C. (Anne-Claire), Wallentin, L.C. (Lars), Waterworth, D. (Dawn), White, H.D. (Harvey D.), Wilson, J.F. (James), Zonderman, A.B., Kathiresan, S. (Sekar), Grarup, N. (Niels), Esko, T. (Tõnu), Loos, R.J.F. (Ruth), Lange, L.A. (Leslie), Faraday, N. (Nauder), Abumrad, N.A. (Nada A.), Edwards, T.L. (Todd L.), Ganesh, S.K. (Santhi), Auer, P. (Paul), Johnson, A.D. (Andrew), Reiner, A. (Alexander), Lettre, G. (Guillaume), Chami, N. (Nathalie), Chen, M.-H. (Ming-Huei), Slater, A.J. (Andrew J.), Eicher, J.D. (John D.), Evangelou, E. (Evangelos), Tajuddin, S.M. (Salman M.), Love-Gregory, L. (Latisha), Kacprowski, T. (Tim), Schick, U.M. (Ursula), Nomura, A. (Akihiro), Giri, A. (Ayush), Lessard, S. (Samuel), Brody, J.A. (Jennifer A.), Schurmann, C. (Claudia), Pankratz, V.S. (Shane), Yanek, L.R. (Lisa), Manichaikul, A. (Ani), Pazoki, R. (Raha), Mihailov, E. (Evelin), Hill, W.D. (W. David), Raffield, L.M. (Laura M.), Burt, A.D. (Alastair), Bartz, T.M. (Traci M.), Becker, D.M. (Diane), Becker, L.C. (Lewis), Boerwinkle, E.A. (Eric), Bork-Jensen, J. (Jette), Bottinger, E.P. (Erwin), O'Donoghue, M.L. (Michelle L.), Crosslin, D.R. (David), de Denus, S. (Simon), Dubé, M.-P. (Marie-Pierre), Elliott, P. (Paul), Engström, G., Evans, M.K. (Michele), Floyd, J. (James), Fornage, M. (Myriam), Gao, H. (He), Greinacher, A. (Andreas), Gudnason, V. (Vilmundur), Hansen, T. (T.), Harris, T.B. (Tamara), Hayward, C. (Caroline), Hernesniemi, J. (Jussi), Highland, H. (Heather), Hirschhorn, J.N. (Joel), Hofman, A. (Albert), Irvin, M.R. (Marguerite R.), Kähönen, M. (Mika), Lange, E.M. (Ethan), Launer, L.J. (Lenore J.), Lehtimäki, T. (Terho), Li, J. (Jin), Liewald, D.C.M. (David), Linneberg, A. (Allan), Liu, Y. (YongMei), Lu, Y. (Yingchang), Lyytikäinen, L.-P. (Leo-Pekka), Mägi, R. (Reedik), Mathias, J. (Jasmine), Melander, O. (Olle), Metspalu, A. (Andres), Mononen, K. (Kari), Nalls, M.A. (Michael), Nickerson, D.A. (Deborah), Nikus, K. (Kjell), O'Donnell, C.J. (Christopher), Orho-Melander, M. (Marju), Pedersen, O. (Oluf), Petersmann, A. (Astrid), Polfus, L. (Linda), Psaty, B.M. (Bruce), Raitakari, O.T. (Olli T.), Raitoharju, E. (Emma), Richard, M. (Melissa), Rice, K.M. (Kenneth), Rivadeneira Ramirez, F. (Fernando), Rotter, J.I. (Jerome I.), Schmidt, F. (Frank), Smith, A.V. (Albert Vernon), Starr, J.M. (John), Taylor, K.D. (Kent), Teumer, A. (Alexander), Thuesen, B.H. (Betina H.), Torstenson, E.S. (Eric S.), Tracy, R.P. (Russell), Tzoulaki, I., Zakai, N.A. (Neil), Vacchi-Suzzi, C. (Caterina), Duijn, C.M. (Cornelia) van, Rooij, F.J.A. (Frank) van, Cushman, M. (Mary Ann), Deary, I.J. (Ian), Velez Edwards, D.R. (Digna R.), Vergnaud, A.-C. (Anne-Claire), Wallentin, L.C. (Lars), Waterworth, D. (Dawn), White, H.D. (Harvey D.), Wilson, J.F. (James), Zonderman, A.B., Kathiresan, S. (Sekar), Grarup, N. (Niels), Esko, T. (Tõnu), Loos, R.J.F. (Ruth), Lange, L.A. (Leslie), Faraday, N. (Nauder), Abumrad, N.A. (Nada A.), Edwards, T.L. (Todd L.), Ganesh, S.K. (Santhi), Auer, P. (Paul), Johnson, A.D. (Andrew), Reiner, A. (Alexander), and Lettre, G. (Guillaume)
- Abstract
Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 × 10−10 for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p < 3 × 10−8 for hematocrit [HCT] and HGB). In African Americans, we identified a nonsense variant in CD36 associated with higher RBC distribut
- Published
- 2016
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