Genomics & Informatics

Korea Genome Organization (한국유전체학회)
권호 표지
DOI QR코드

DOI QR Code

A Genome-wide Association Study of Copy Number Variation in Hematological Parameters in the Korean Population

  • Kim, Ka-Kyung (Samsung Biomedical Research Institute, Samsung Medical Center) ;
  • Cho, Yoon-Shin (Center for Genome Science, National Institute of Health) ;
  • Cho, Nam-H. (Department of Preventive Medicine, Ajou University School of Medicine) ;
  • Shin, Chol (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Korea University Ansan Hospital) ;
  • Kim, Jong-Won (Department of Laboratory Medicine and Genetics, Sungkyunkwan University School of Medicine, Samsung Medical Center)
  • Accepted : 2010.09.15
  • Published : 2010.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Abnormal hematological values are associated with various disorders including cancer and cardiovascular, metabolic, infectious, and immune diseases. We report the copy number variations (CNVs) in clinically relevant hematological parameters, including hemoglobin level, red and white blood cell counts, platelet counts, and red blood cell (RBC) volume. We describe CNVs in several loci associated with these hematological parameters in 8,842 samples from Korean population-based studies. The data that we evaluated included four RBC parameters, one platelet parameter, and one associated with total white blood cell (WBC) count, exceeding the genome-wide significance. We show that CNVs in hematological parameters are associated with some loci, different from previously associated loci reported in single nucleotide polymorphism (SNP) association studies.

Keywords

References

  1. Cho, Y.S., Go, M.J., Kim, Y.J., Heo, J.Y., Oh, J.H., Ban, H.J., Yoon, D., Lee, M.H., Kim, D.J., Park, M., Cha, S.H., Kim, J.W., Han, B.G., Min, H., Ahn, Y., Park, M.S., Han, H.R., Jang, H.Y., Cho, E.Y., Lee, J.E., Cho, N.H., Shin, C., Park, T., Park, J.W., Lee, J.K., Cardon, L., Clarke, G., McCarthy, M.I., Lee, J.Y., Lee, J.K., Oh, B., and Kim, H.L. (2009). A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits. Nat. Genet. 41, 527-534. https://doi.org/10.1038/ng.357
  2. Colella, S., Yau, C., Taylor, J.M., Mirza, G., Butler, H., Clouston, P., Bassett, A.S., Seller, A., Holmes, C.C., and Ragoussis, J. (2007). QuantiSNP: an Objective Bayes Hidden-Markov Model to detect and accurately map copy number variation using SNP genotyping data. Nucl. Acids Res. 35, 2013-2025. https://doi.org/10.1093/nar/gkm076
  3. Conrad, D.F., Pinto, D., Redon, R., Feuk, L., Gokcumen, O., Zhang, Y., Aerts, J., Andrews, T.D., Barnes, C., Campbell, P., Fitzgerald, T., Hu, M., Ihm, C.H., Kristiansson, K., Macarthur, D.G., Macdonald, J.R., Onyiah, I., Pang, A.W., Robson, S., Stirrups, K., Valsesia, A., Walter, K., Wei, J., Tyler-Smith, C., Carter, N.P., Lee, C., Scherer, S.W., and Hurles, M.E. (2010). Origins and functional impact of copy number variation in the human genome. Nature 464, 704-712. https://doi.org/10.1038/nature08516
  4. Craddock, N., Hurles, M.E., Cardin, N., Pearson, R.D., Plagnol, V., Robson, S., Vukcevic, D., Barnes, C., Conrad, D.F., Giannoulatou, E., Holmes, C., Marchini, J.L., Stirrups, K., Tobin, M.D., Wain, L.V., Yau, C., Aerts, J., Ahmad, T., Andrews, T.D., Arbury, H., Attwood, A., Auton, A., Ball, S.G., Balmforth, A.J., Barrett, J.C., Barroso, I., Barton, A., Bennett, A.J., Bhaskar, S., Blaszczyk, K., Bowes, J., Brand, O.J., Braund, P.S., Bredin, F., Breen, G., Brown, M.J., Bruce, I.N., Bull, J., Burren, O.S., Burton, J., Byrnes, J., Caesar, S., Clee, C.M., Coffey, A.J., Connell, J.M., Cooper, J.D., Dominiczak, A.F., Downes, K., Drummond, H.E., Dudakia, D., Dunham, A., Ebbs, B., Eccles, D., Edkins, S., Edwards, C., Elliot, A., Emery, P., Evans, D.M., Evans, G., Eyre, S., Farmer, A., Ferrier, I.N., Feuk, L., Fitzgerald, T., Flynn, E., Forbes, A., Forty, L., Franklyn, J.A., Freathy, R.M., Gibbs, P., Gilbert, P., Gokumen, O., Gordon-Smith, K., Gray, E., Green, E., Groves, C.J., Grozeva, D., Gwilliam, R., Hall, A., Hammond, N., Hardy, M., Harrison, P., Hassanali, N., Hebaishi, H., Hines, S., Hinks, A., Hitman, G.A., Hocking, L., Howard, E., Howard, P., Howson, J.M., Hughes, D., Hunt, S., Isaacs, J.D., Jain, M., Jewell, D.P., Johnson, T., Jolley, J.D., Jones, I.R., Jones, L.A., Kirov, G., Langford, C.F., Lango-Allen, H., Lathrop, G.M., Lee, J., Lee, K.L., Lees, C., Lewis, K., Lindgren, C.M., Maisuria-Armer, M., Maller, J., Mansfield, J., Martin, P., Massey, D.C., McArdle, W.L., McGuffin, P., McLay, K.E., Mentzer, A., Mimmack, M.L., Morgan, A.E., Morris, A.P., Mowat, C., Myers, S., Newman, W., Nimmo, E.R., O'Donovan, M.C., Onipinla, A., Onyiah, I., Ovington, N.R., Owen, M.J., Palin, K., Parnell, K., Pernet, D., Perry, J.R., Phillips, A., Pinto, D., Prescott, N.J., Prokopenko, I., Quail, M.A., Rafelt, S., Rayner, N.W., Redon, R., Reid, D.M., Renwick, Ring, S.M., Robertson, N., Russell, E., St Clair, D., Sambrook, J.G., Sanderson, J.D., Schuilenburg, H., Scott, C.E., Scott, R., Seal, S., Shaw-Hawkins, S., Shields, B.M., Simmonds, M.J., Smyth, D.J., Somaskantharajah, E., Spanova, K., Steer, S., Stephens, J., Stevens, H.E., Stone, M.A., Su, Z., Symmons, D.P., Thompson, J.R., Thomson, W., Travers, M.E., Turnbull, C., Valsesia, A., Walker, M., Walker, N.M., Wallace, C., Warren-Perry, M., Watkins, N.A., Webster, J., Weedon, M.N., Wilson, A.G., Woodburn, M., Wordsworth, B.P., Young, A.H., Zeggini, E., Carter, N.P., Frayling, T.M., Lee, C., McVean, G., Munroe, P.B., Palotie, A., Sawcer, S.J., Scherer, S.W., Strachan, D.P., Tyler-Smith, C., Brown, M.A., Burton, P.R., Caulfield, M.J., Compston, A., Farrall, M., Gough, S.C., Hall, A.S., Hattersley, A.T., Hill, A.V., Mathew, C.G., Pembrey, M., Satsangi, J., Stratton, M.R., Worthington, J., Deloukas, P., Duncanson, A., Kwiatkowski, D.P., McCarthy, M.I., Ouwehand, W., Parkes, M., Rahman, N., Todd, J.A., Samani, N.J., and Donnelly, P. (2010). Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls. Nature 464, 713-720. https://doi.org/10.1038/nature08979
  5. Ferreira, M.A., Hottenga, J.J., Warrington, N.M., Medland, S.E., Willemsen, G., Lawrence, R.W., Gordon, S., de Geus, E.J., Henders, A.K., Smit, J.H., Campbell, M.J., Wallace, L., Evans, D.M., Wright, M.J., Nyholt, D.R., James, A.L., Beilby, J.P., Penninx, B.W., Palmer, L.J., Frazer, I.H., Montgomery, G.W., Martin, N.G., and Boomsma, D.I. (2009). Sequence variants in three loci influence monocyte counts and erythrocyte volume. Am. J. Hum. Genet. 85, 745-749. https://doi.org/10.1016/j.ajhg.2009.10.005
  6. Ganesh, S.K., Zakai, N.A., van Rooij, F.J., 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., Verwoert, G.C., Teumer, A., Fox, C.S., Guralnik, J.M., Ehret, G.B., Rice, K., Felix, J.F., Rendon, A., Eiriksdottir, G., Levy, D., Patel, K.V., Boerwinkle, E., Rotter, J.I., Hofman, A., Sambrook, J.G., Hernandez, D.G., Zheng, G., Bandinelli, S., Singleton, A.B., Coresh, J., Lumley, T., Uitterlinden, A.G., Vangils, J.M., Launer, L.J., Cupples, L.A., Oostra, B.A., Zwaginga, J.J., Ouwehand, W.H., Thein, S.L., Meisinger, C., Deloukas, P., Nauck, M., Spector, T.D., Gieger, C., Gudnason, V., van Duijn, C.M., Psaty, B.M., Ferrucci, L., Chakravarti, A., Greinacher, A., O'Donnell, C.J., Witteman, J.C., Furth, S., Cushman, M., Harris, T.B., and Lin, J.P. (2009). Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium. Nat. Genet. 41, 1191-1198. https://doi.org/10.1038/ng.466
  7. Iafrate, A.J., Feuk, L., Rivera, M.N., Listewnik, M.L., Donahoe, P.K., Qi, Y., Scherer, S.W., and Lee, C. (2004). Detection of large-scale variation in the human genome. Nat. Genet. 36, 949-951. https://doi.org/10.1038/ng1416
  8. Kamatani, Y., Matsuda, K., Okada, Y., Kubo, M., Hosono, N., Daigo, Y., Nakamura, Y., and Kamatani, N. (2010). Genome-wide association study of hematological and biochemical traits in a Japanese population. Nat. Genet. 42, 210-215. https://doi.org/10.1038/ng.531
  9. McCarroll, S.A., Kuruvilla, F.G., Korn, J.M., Cawley, S., Nemesh, J., Wysoker, A., Shapero, M.H., de Bakker, P.I., Maller, J.B., Kirby, A., Elliott, A.L., Parkin, M., Hubbell, E., Webster, T., Mei, R., Veitch, J., Collins, P.J., Handsaker, R., Lincoln, S., Nizzari, M., Blume, J., Jones, K.W., Rava, R., Daly, M.J., Gabriel, S.B., and Altshuler, D. (2008). Integrated detection and population-genetic analysis of SNPs and copy number variation. Nat. Genet. 40, 1166-1174. https://doi.org/10.1038/ng.238
  10. Soranzo, N., Spector, T.D., Mangino, M., Kuhnel, B., Rendon, A., Teumer, A., Willenborg, C., Wright, B., Chen, L., Li, M., Salo, P., Voight, B.F., Burns, P., Laskowski, R.A., Xue, Y., Menzel, S., Altshuler, D., Bradley, J.R., Bumpstead, S., Burnett, M.S., Devaney, J., Doring, A., Elosua, R., Epstein, S.E., Erber, W., Falchi, M., Garner, S.F., Ghori, M.J., Goodall, A.H., Gwilliam, R., Hakonarson, H.H., Hall, A.S., Hammond, N., Hengstenberg, C., Illig, T., Konig, I.R., Knouff, C.W., McPherson, R., Melander, O., Mooser, V., Nauck, M., Nieminen, M.S., O'Donnell, C.J., Peltonen, L., Potter, S.C., Prokisch, H., Rader, D.J., Rice, C.M., Roberts, R., Salomaa, V., Sambrook, J., Schreiber, S., Schunkert, H., Schwartz, S.M., Serbanovic-Canic, J., Sinisalo, J., Siscovick, D.S., Stark, K., Surakka, I., Stephens, J., Thompson, J.R., Volker, U., Volzke, H., Watkins, N.A., Wells, G.A., Wichmann, H.E., Van Heel, D.A., Tyler-Smith, C., Thein, S.L., Kathiresan, S., Perola, M., Reilly, M.P., Stewart, A.F., Erdmann, J., Samani, N.J., Meisinger, C., Greinacher, A., Deloukas, P., Ouwehand, W.H., and Gieger, C. (2009). A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium. Nat. Genet. 41, 1182-1190. https://doi.org/10.1038/ng.467
  11. Wang, K., Li, M., Hadley, D., Liu, R., Glessner, J., Grant, S.F., Hakonarson, H., and Bucan, M. (2007). PennCNV: an integrated hidden Markov model designed for high-resolution copy number variation detection in whole-genome SNP genotyping data. Genome Res. 17, 1665-1674. https://doi.org/10.1101/gr.6861907
  12. Yim, S.H., Kim, T.M., Hu, H.J., Kim, J.H., Kim, B.J., Lee, J.Y., Han, B.G., Shin, S.H., Jung, S.H., and Chung, Y.J. (2010). Copy number variations in East-Asian population and their evolutionary and functional implications. Hum. Mol. Genet. 19, 1001-1008. https://doi.org/10.1093/hmg/ddp564

Cited by

  1. Genome-Wide Association Studies of the Korea Association REsource (KARE) Consortium vol.8, pp.3, 2010, https://doi.org/10.5808/GI.2010.8.3.101