Genome-wide Survey of Copy Number Variants Associated with Blood Pressure and Body Mass Index in a Korean Population

  • Moon, Sang-Hoon (Division of Structural and Functional Genomics, Center for Genome Science, Korea National Institute of Health) ;
  • Kim, Young-Jin (Division of Structural and Functional Genomics, Center for Genome Science, Korea National Institute of Health) ;
  • Kim, Yun-Kyoung (Division of Structural and Functional Genomics, Center for Genome Science, Korea National Institute of Health) ;
  • Kim, Dong-Joon (Division of Structural and Functional Genomics, Center for Genome Science, Korea National Institute of Health) ;
  • Lee, Ji-Young (Division of Structural and Functional Genomics, Center for Genome Science, Korea National Institute of Health) ;
  • Go, Min-Jin (Division of Structural and Functional Genomics, Center for Genome Science, Korea National Institute of Health) ;
  • Shin, Young-Ah (Division of Structural and Functional Genomics, Center for Genome Science, Korea National Institute of Health) ;
  • Hong, Chang-Bum (Division of Structural and Functional Genomics, Center for Genome Science, Korea National Institute of Health) ;
  • Kim, Bong-Jo (Division of Structural and Functional Genomics, Center for Genome Science, Korea National Institute of Health)
  • Received : 2011.11.11
  • Accepted : 2011.12.09
  • Published : 2011.12.31


Hypertension is the major factor of most death and high blood pressure (BP) can lead to stroke, myocardial infarction and cardiac failure. Moreover, hypertension is strongly correlated with body mass index (BMI). Although the exact causes of hypertension are still unclear, some of genetic loci were discovered from genome-wide association study (GWAS). Therefore, it is essential to study genetic variation for finding more genetic factor affecting hypertension. The purpose of our study is to conduct a CNV association study for hypertension-related traits, BP and BMI, in Korean individuals. We identified 2,206 CNV regions from 3,274 community-based Korean participants using the Affymetrix Genome-Wide Human SNP Array 6.0 platform and performed a logistic regression analysis of CNVs with two hypertension-related traits, BP and BMI. Moreover, the 4,692 participants in an independent cohort were selected for respective replication analyses. GWAS of CNV identified two loci encompassing previously known hypertension-related genes: LPA (lipoprotein) on 6q26, and JAK2 (Janus kinase 2) on 9p24, with suggestive p-values (0.0334 for LPA and 0.0305 for JAK2 ). These two positive findings, however, were not evaluated in the replication stage. Our result confirmed the conclusion of CNV study from the WTCCC suggesting weak association with common diseases. This is the first study of CNV association study with BP and BMI in Korean population and it provides a state of CNV association study with common human diseases using SNP array.


copy number variation;hypertension-related traits;BMI;blood pressure;genome-wide association study


Supported by : Korea National Institute of Health, Korea Centers for Disease Control and Prevention


  1. Loos, R.J., Lindgren, C.M., Li, S., Wheeler, E., Zhao, J.H., Prokopenko, I., Inouye, M., Freathy, R.M., Attwood, A.P., Beckmann, J.S., Berndt, S.I., Prostate, L.C., Ovarian Cancer Screening, T., Jacobs, K.B., Chanock, S.J., Hayes, R.B., Bergmann, S., Bennett, A.J., Bingham, S.A., Bochud, M., Brown, M., Cauchi, S., Connell, J.M., Cooper, C., Smith, G.D., Day, I., Dina, C., De, S., Dermitzakis, E.T., Doney, A.S., Elliott, K.S., Elliott, P., Evans, D.M., Sadaf Farooqi, I., Froguel, P., Ghori, J., Groves, C.J., Gwilliam, R., Hadley, D., Hall, A.S., Hattersley, A.T., Hebebrand, J., Heid, I.M., KORA, Lamina, C., Gieger, C., Illig, T., Meitinger, T., Wichmann, H.E., Herrera, B., Hinney, A., Hunt, S.E., Jarvelin, M.R., Johnson, T., Jolley, J.D., Karpe, F., Keniry, A., Khaw, K.T., Luben, R.N., Mangino, M., Marchini, J., McArdle, W.L., McGinnis, R., Meyre, D., Munroe, P.B., Morris, A.D., Ness, A.R., Neville, M.J., Nica, A.C., Ong, K.K., O'Rahilly, S., Owen, K.R., Palmer, C.N., Papadakis, K., Potter, S., Pouta, A., Qi, L., Nurses' Health, S., Randall, J.C., Rayner, N.W., Ring, S.M., Sandhu, M.S., Scherag, A., Sims, M.A., Song, K., Soranzo, N., Speliotes, E.K., Diabetes Genetics, I., Syddall, H.E., Teichmann, S.A., Timpson, N.J., Tobias, J.H., Uda, M., Sardi, N.I.A.S., Vogel, C.I., Wallace, C., Waterworth, D.M., Weedon, M.N., Wellcome Trust Case Control, C., Willer, C.J., Fusion, Wraight, Yuan, X., Zeggini, E., Hirschhorn, J.N., Strachan, D.P., Ouwehand, W.H., Caulfield, M.J., Samani, N.J., Frayling, T.M., Vollenweider, P., Waeber, G., Mooser, V., Deloukas, P., McCarthy, M.I., Wareham, N.J., Barroso, I., Jacobs, K.B., Chanock, S.J., Hayes, R.B., Lamina, C., Gieger, C., Illig, T., Meitinger, T., Wichmann, H.E., Kraft, P., Hankinson, S.E., Hunter, D.J., Hu, F.B., Lyon, H.N., Voight, B.F., Ridderstrale, M., Groop, L., Scheet, P., Sanna, S., Abecasis, G.R., Albai, G., Nagaraja, R., Schlessinger, D., Jackson, A.U., Tuomilehto, J., Collins, F.S., Boehnke, M., and Mohlke, K.L. (2008). Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat. Genet. 40, 768-775.
  2. Charchar, F.J., Kaiser, M., Bingham, A.J., Fotinatos, N., Ahmady, F., Tomaszewski, M., and Samani, N.J. (2010), Whole-genome survey of copy number variation in the Spontaneously Hypertensive Rat: Relationship to quantitative trait loci, gene expression, and blood pressure. Hypertension 55, 1231-1238.
  3. 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.
  4. Deo, R.C., Wilson, J.G., Xing, C., Lawson, K., Kao, W.H., Reich, D., Tandon, A., Akylbekova, E., Patterson, N., Mosley, T.H., Jr., Boerwinkle, E., and Taylor, H.A., Jr. (2011). Single-nucleotide polymorphisms in LPA explain most of the ancestry-specific variation in Lp(a) levels in African Americans. PLoS One 6, e14581.
  5. Dorajoo, R., Blakemore, A.I., Sim, X., Ong, R.T., Ng, D.P., Seielstad, M., Wong, T.Y., Saw, S.M., Froguel, P., Liu, J., and Tai, E.S. (2011). Replication of 13 obesity loci among Singaporean Chinese, Malay and Asian-Indian populations. Int. J . Obes. [Epub ahead of print].
  6. Estivill, X. and Armengol, L. (2007). Copy number variants and common disorders: filling the gaps and exploring complexity in genome-wide association studies. PLoS Genet. 3, 1787-1799.
  7. Frayling, T.M., Timpson, N.J., Weedon, M.N., Zeggini, E., Freathy, R.M., Lindgren, C.M., Perry, J.R., Elliott, K.S., Lango, H., Rayner, N.W., Shields, B., Harries, L.W., Barrett, J.C., Ellard, S., Groves, C.J., Knight, B., Patch, A.M., Ness, A.R., Ebrahim, S., Lawlor, D.A., Ring, S.M., Ben-Shlomo, Y., Jarvelin, M.R., Sovio, U., Bennett, A.J., Melzer, D., Ferrucci, L., Loos, R.J., Barroso, I., Wareham, N.J., Karpe, F., Owen, K.R., Cardon, L.R., Walker, M., Hitman, G.A., Palmer, C.N., Doney, A.S., Morris, A.D., Smith, G.D., Hattersley, A.T., and McCarthy, M.I. (2007). A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316, 889-894.
  8. Freeman, J.L., Perry, G.H., Feuk, L., Redon, R., McCarroll, S.A., Altshuler, D.M., Aburatani, H., Jones, K.W., Tyler-Smith, C., Hurles, M.E., Carter, N.P., Scherer, S.W., and Lee, C. (2006). Copy number variation: new insights in genome diversity. Genome Res. 16, 949-961.
  9. Glessner, J.T., Bradfield, J.P., Wang, K., Takahashi, N., Zhang, H., Sleiman, P.M., Mentch, F.D., Kim, C.E., Hou, C., Thomas, K.A., Garris, M.L., Deliard, S., Frackelton, E.C., Otieno, F.G., Zhao, J., Chiavacci, R.M., Li, M., Buxbaum, J.D., Berkowitz, R.I., Hakonarson, H., and Grant, S.F. (2010). A genome-wide study reveals copy number variants exclusive to childhood obesity cases. Am. J. Hum. Genet. 87, 661-666.
  10. Guilluy, C., Bregeon, J., Toumaniantz, G., Rolli-Derkinderen, M., Retailleau, K., Loufrani, L., Henrion, D., Scalbert, E., Bril, A., Torres, R.M., Offermanns, S., Pacaud, P., and Loirand, G. (2010). The Rho exchange factor Arhgef1 mediates the effects of angiotensin II on vascular tone and blood pressure. Nat. Med. 16, 183-190.
  11. Hong, K.W., Jin, H.S., Cho, Y.S., Lee, J.Y., Lee, J.E., Cho, N.H., Shin, C., Lee, S.H., Park, H.K., and Oh, B. (2009). Replication of the Wellcome Trust genome-wide association study on essential hypertension in a Korean population. Hypertens. Res. 32, 570-574.
  12. Johnson, J.A., Vnencak-Jones, C.L., Cogan, J.D., Loyd, J.E., and West, J. (2009). Copy-number variation in BMPR2 is not associated with the pathogenesis of pulmonary arterial hypertension. BMC Med. Genet. 10, 58.
  13. Kato, N., Takeuchi, F., Tabara, Y., Kelly, T.N., Go, M.J., Sim, X., Tay, W.T., Chen, C.H., Zhang, Y., Yamamoto, K., Katsuya, T., Yokota, M., Kim, Y.J., Ong, R.T., Nabika, T., Gu, D., Chang, L.C., Kokubo, Y., Huang, W., Ohnaka, K., Yamori, Y., Nakashima, E., Jaquish, C.E., Lee, J.Y., Seielstad, M., Isono, M., Hixson, J.E., Chen, Y.T., Miki, T., Zhou, X., Sugiyama, T., Jeon, J.P., Liu, J.J., Takayanagi, R., Kim, S.S., Aung, T., Sung, Y.J., Zhang, X., Wong, T.Y., Han, B.G., Kobayashi, S., Ogihara, T., Zhu, D., Iwai, N., Wu, J.Y., Teo, Y.Y., Tai, E.S., Cho, Y.S., and He, J. (2011). Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians. Nat. Genet. 43, 531-538.
  14. Komura, D., Shen, F., Ishikawa, S., Fitch, K.R., Chen, W., Zhang, J., Liu, G., Ihara, S., Nakamura, H., Hurles, M.E., Lee, C., Scherer, S.W., Jones, K.W., Shapero, M.H., Huang, J., and Aburatani, H. (2006). Genome-wide detection of human copy number variations using high-density DNA oligonucleotide arrays. Genome Res. 16, 1575-1584.
  15. Levy, D., Ehret, G.B., Rice, K., Verwoert, G.C., Launer, L.J., Dehghan, A., Glazer, N.L., Morrison, A.C., Johnson, A.D., Aspelund, T., Aulchenko, Y., Lumley, T., Kottgen, A., Vasan, R.S., Rivadeneira, F., Eiriksdottir, G., Guo, X., Arking, D.E., Mitchell, G.F., Mattace-Raso, F.U., Smith, A.V., Taylor, K., Scharpf, R.B., Hwang, S.J., Sijbrands, E.J., Bis, J., Harris, T.B., Ganesh, S.K., O'Donnell, C.J., Hofman, A., Rotter, J.I., Coresh, J., Benjamin, E.J., Uitterlinden, A.G., Heiss, G., Fox, C.S., Witteman, J.C., Boerwinkle, E., Wang, T.J., Gudnason, V., Larson, M.G., Chakravarti, A., Psaty, B.M., and van Duijn, C.M. (2009). Genome-wide association study of blood pressure and hypertension. Nat. Genet. 41, 677-687.
  16. Marioni, J.C., Thorne, N.P., Valsesia, A., Fitzgerald, T., Redon, R., Fiegler, H., Andrews, T.D., Stranger, B.E., Lynch, A.G., Dermitzakis, E.T., Carter, N.P., Tavare, S., and Hurles, M.E. (2007). Breaking the waves: improved detection of copy number variation from microarray-based comparative genomic hybridization. Genome Biol. 8, R228.
  17. 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.
  18. Newton-Cheh, C., Johnson, T., Gateva, V., Tobin, M.D., Bochud, M., Coin, L., Najjar, S.S., Zhao, J.H., Heath, S.C., Eyheramendy, S., Papadakis, K., Voight, B.F., Scott, L.J., Zhang, F., Farrall, M., Tanaka, T., Wallace, C., Chambers, J.C., Khaw, K.T., Nilsson, P., van der Harst, P., Polidoro, S., Grobbee, D.E., Onland-Moret, N.C., Bots, M.L., Wain, L.V., Elliott, K.S., Teumer, A., Luan, J., Lucas, G., Kuusisto, J., Burton, P.R., Hadley, D., McArdle, W.L., Wellcome Trust Case Control, C., Brown, M., Dominiczak, A., Newhouse, S.J., Samani, N.J., Webster, J., Zeggini, E., Beckmann, J.S., Bergmann, S., Lim, N., Song, K., Vollenweider, P., Waeber, G., Waterworth, D.M., Yuan, X., Groop, L., Orho-Melander, M., Allione, A., Di Gregorio, A., Guarrera, S., Panico, S., Ricceri, F., Romanazzi, V., Sacerdote, C., Vineis, P., Barroso, I., Sandhu, M.S., Luben, R.N., Crawford, G.J., Jousilahti, P., Perola, M., Boehnke, M., Bonnycastle, L.L., Collins, F.S., Jackson, A.U., Mohlke, K.L., Stringham, H.M., Valle, T.T., Willer, C.J., Bergman, R.N., Morken, M.A., Doring, A., Gieger, C., Illig, T., Meitinger, T., Org, E., Pfeufer, A., Wichmann, H.E., Kathiresan, S., Marrugat, J., O'Donnell, C.J., Schwartz, S.M., Siscovick, D.S., Subirana, I., Freimer, N.B., Hartikainen, A.L., McCarthy, M.I., O'Reilly, P.F., Peltonen, L., Pouta, A., de Jong, P.E., Snieder, H., van Gilst, W.H., Clarke, R., Goel, A., Hamsten, A., Peden, J.F., Seedorf, U., Syvanen, A.C., Tognoni, G., Lakatta, E.G., Sanna, S., Scheet, P., Schlessinger, D., Scuteri, A., Dorr, M., Ernst, F., Felix, S.B., Homuth, G., Lorbeer, R., Reffelmann, T., Rettig, R., Volker, U., Galan, P., Gut, I.G., Hercberg, S., Lathrop, G.M., Zelenika, D., Deloukas, P., Soranzo, N., Williams, F.M., Zhai, G., Salomaa, V., Laakso, M., Elosua, R., Forouhi, N.G., Volzke, H., Uiterwaal, C.S., van der Schouw, Y.T., Numans, M.E., Matullo, G., Navis, G., Berglund, G., Bingham, S.A., Kooner, J.S., Connell, J.M., Bandinelli, S., Ferrucci, L., Watkins, H., Spector, T.D., Tuomilehto, J., Altshuler, D., Strachan, D.P., Laan, M., Meneton, P., Wareham, N.J., Uda, M., Jarvelin, M.R., Mooser, V., Melander, O., Loos, R.J., Elliott, P., Abecasis, G.R., Caulfield, M., and Munroe, P.B. (2009). Genome-wide association study identifies eight loci associated with blood pressure. Nat. Genet. 41, 666-676.
  19. Olsen, A.B., and Venkatraman, E.S. (2004). Circular binary segmentation for the analysis of array-based DNA copy number data. Biostatistics 5, 557-572.
  20. Pique-Regi, R., Monso-Varona, J., Ortega, A., Seeger, R.C., Triche, T.J., and Asgharzadeh, S. (2008). Sparse representation and Bayesian detection of genome copy number alterations from microarray data. Bioinformatics 24, 309-318.
  21. Wellcome Trust Case Control Consortium, 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.
  22. Redon, R., Ishikawa, S., Fitch, K.R., Feuk, L., Perry, G.H., Andrews, T.D., Fiegler, H., Shapero, M.H., Carson, A.R., Chen, W., Cho, E.K., Dallaire, S., Freeman, J.L., Gonzalez, J.R., Gratacos, M., Huang, J., Kalaitzopoulos, D., Komura, D., MacDonald, J.R., Marshall, C.R., Mei, R., Montgomery, L., Nishimura, K., Okamura, K., Shen, F., Somerville, M.J., Tchinda, J., Valsesia, A., Woodwark, C., Yang, F., Zhang, J., Zerjal, T., Zhang, J., Armengol, L., Conrad, D.F., Estivill, X., Tyler-Smith, C., Carter, N.P., Aburatani, H., Lee, C., Jones, K.W., Scherer, S.W., and Hurles, M.E. (2006). Global variation in copy number in the human genome. Nature 444, 444-454.
  23. Sha, B.Y., Yang, T.L., Zhao, L.J., Chen, X.D., Guo, Y., Chen, Y., Pan, F., Zhang, Z.X., Dong, S.S., Xu, X.H., and Deng, H.W. (2009). Genome-wide association study suggested copy number variation may be associated with body mass index in the Chinese population. J. Hum. Genet. 54, 199-202.
  24. The Welcome Trust Case Control Consortium. (2007). Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661-678.
  25. Thomas, P.D., Campbell, M.J., Kejariwal, A., Mi, H., Karlak, B., Daverman, R., Diemer, K., Muruganujan, A. and Narechania, A. (2003). PANTHER: a library of protein families and subfamilies indexed by function. Genome Res. 13, 2129-2141.
  26. van der Hoek, Y.Y., Wittekoek, M.E., Beisiegel, U., Kastelein, J.J., and Koschinsky, M.L. (1993). The apolipoprotein( a) kringle IV repeats which differ from the major repeat kringle are present in variably-sized isoforms. Hum. Mol. Genet. 2, 361-366.
  27. Wong, K.K., deLeeuw, R.J., Dosanjh, N.S., Kimm, L.R., Cheng, Z., Horsman, D.E., MacAulay, C., Ng, R.T., Brown, C.J., Eichler, E.E., and Lam, W.L. (2007). A comprehensive analysis of common copy-number variations in the human genome. Am . J. Hum. Genet. 80, 91-104.
  28. Yu, W., Gwinn, M., Clyne, M., Yesupriya, A., and Khoury, M.J. (2008). A navigator for human genome epidemiology. Nat. Genet. 40, 124-125.