Defining the role of common variation in the genomic and biological architecture of adult human height

Wood, A. R. et al. (2014) Defining the role of common variation in the genomic and biological architecture of adult human height. Nature Genetics, 46(11), pp. 1173-1186. (doi:10.1038/ng.3097)

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Abstract

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ~2,000, ~3,700 and ~9,500 SNPs explained ~21%, ~24% and ~29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate–related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Stott, Professor David J and Ford, Professor Ian and Strawbridge, Dr Rona
Authors: Wood, A. R., Esko, T., Yang, J., Vedantam, S., Pers, T. H., Gustafsson, S., Chu, A. Y., Estrada, K., Luan, J.'a., Kutalik, Z., Amin, N., Buchkovich, M. L., Croteau-Chonka, D. C., Day, F. R., Duan, Y., Fall, T., Fehrmann, R., Ferreira, T., Jackson, A. U., Karjalainen, J., Lo, K. S., Locke, A. E., Mägi, R., Mihailov, E., Porcu, E., Randall, J. C., Scherag, A., Vinkhuyzen, A. A. E., Westra, H.-J., Winkler, T. W., Workalemahu, T., Zhao, J. H., Absher, D., Albrecht, E., Anderson, D., Baron, J., Beekman, M., Demirkan, A., Ehret, G. B., Feenstra, B., Feitosa, M. F., Fischer, K., Fraser, R. M., Goel, A., Gong, J., Justice, A. E., Kanoni, S., Kleber, M. E., Kristiansson, K., Lim, U., Lotay, V., Lui, J. C., Mangino, M., Leach, I. M., Medina-Gomez, C., Nalls, M. A., Nyholt, D. R., Palmer, C. D., Pasko, D., Pechlivanis, S., Prokopenko, I., Ried, J. S., Ripke, S., Shungin, D., Stancáková, A., Strawbridge, R. J., Sung, Y. J., Tanaka, T., Teumer, A., Trompet, S., van der Laan, S. W., van Setten, J., Van Vliet-Ostaptchouk, J. V., Wang, Z., Yengo, L., Zhang, W., Afzal, U., Ärnlöv, J., Arscott, G. M., Bandinelli, S., Barrett, A., Bellis, C., Bennett, A. J., Berne, C., Blüher, M., Bolton, J. L., Böttcher, Y., Boyd, H. A., Bruinenberg, M., Buckley, B. M., Buyske, S., Caspersen, I. H., Chines, P. S., Clarke, R., Claudi-Boehm, S., Cooper, M., Daw, E. W., De Jong, P. A., Deelen, J., Delgado, G., Denny, J. C., Dhonukshe-Rutten, R., Dimitriou, M., Doney, A. S. F., Dörr, M., Eklund, N., Eury, E., Folkersen, L., Garcia, M. E., Geller, F., Giedraitis, V., Go, A. S., Grallert, H., Grammer, T. B., Gräßler, J., Grönberg, H., de Groot, L. C. P. G. M., Groves, C. J., Haessler, J., Hall, P., Haller, T., Hallmans, G., Hannemann, A., Hartman, C. A., Hassinen, M., Hayward, C., Heard-Costa, N. L., Helmer, Q., Hemani, G., Henders, A. K., Hillege, H. L., Hlatky, M. A., Hoffmann, W., Hoffmann, P., Holmen, O., Houwing-Duistermaat, J. J., Illig, T., Isaacs, A., James, A. L., Jeff, J., Johansen, B., Johansson, Å., Jolley, J., Juliusdottir, T., Junttila, J., Kho, A. N., Kinnunen, L., Klopp, N., Kocher, T., Kratzer, W., Lichtner, P., Lind, L., Lindström, J., Lobbens, S., Lorentzon, M., Lu, Y., Lyssenko, V., Magnusson, P. K. E., Mahajan, A., Maillard, M., McArdle, W. L., McKenzie, C. A., McLachlan, S., McLaren, P. J., Menni, C., Merger, S., Milani, L., Moayyeri, A., Monda, K. L., Morken, M. A., Müller, G., Müller-Nurasyid, M., Musk, A. W., Narisu, N., Nauck, M., Nolte, I. M., Nöthen, M. M., Oozageer, L., Pilz, S., Rayner, N. W., Renstrom, F., Robertson, N. R., Rose, L. M., Roussel, R., Sanna, S., Scharnagl, H., Scholtens, S., Schumacher, F. R., Schunkert, H., Scott, R. A., Sehmi, J., Seufferlein, T., Shi, J., Silventoinen, K., Smit, J. H., Smith, A. V., Smolonska, J., Stanton, A. V., Stirrups, K., Stott, D. J., Stringham, H. M., Sundström, J., Swertz, M. A., Syvänen, A.-C., Tayo, B. O., Thorleifsson, G., Tyrer, J. P., van Dijk, S., van Schoor, N. M., van der Velde, N., van Heemst, D., van Oort, F. V. A., Vermeulen, S. H., Verweij, N., Vonk, J. M., Waite, L. L., Waldenberger, M., Wennauer, R., Wilkens, L. R., Willenborg, C., Wilsgaard, T., Wojczynski, M. K., Wong, A., Wright, A. F., Zhang, Q., Arveiler, D., Bakker, S. J. L., Beilby, J., Bergman, R. N., Bergmann, S., Biffar, R., Blangero, J., Boomsma, D. I., Bornstein, S. R., Bovet, P., Brambilla, P., Brown, M. J., Campbell, H., Caulfield, M. J., Chakravarti, A., Collins, R., Collins, F. S., Crawford, D. C., Cupples, L. A., Danesh, J., de Faire, U., den Ruijter, H. M., Erbel, R., Erdmann, J., Eriksson, J. G., Farrall, M., Ferrannini, E., Ferrières, J., Ford, I., Forouhi, N. G., Forrester, T., Gansevoort, R. T., Gejman, P. V., Gieger, C., Golay, A., Gottesman, O., Gudnason, V., Gyllensten, U., Haas, D. W., Hall, A. S., Harris, T. B., Hattersley, A. T., Heath, A. C., Hengstenberg, C., Hicks, A. A., Hindorff, L. A., Hingorani, A. D., Hofman, A., Hovingh, G. K., Humphries, S. E., Hunt, S. C., Hypponen, E., Jacobs, K. B., Jarvelin, M.-R., Jousilahti, P., Jula, A. M., Kaprio, J., Kastelein, J. J. P., Kayser, M., Kee, F., Keinanen-Kiukaanniemi, S. M., Kiemeney, L. A., Kooner, J. S., Kooperberg, C., Koskinen, S., Kovacs, P., Kraja, A. T., Kumari, M., Kuusisto, J., Lakka, T. A., Langenberg, C., Le Marchand, L., Lehtimäki, T., Lupoli, S., Madden, P. A. F., Männistö, S., Manunta, P., Marette, A., Matise, T. C., McKnight, B., Meitinger, T., Moll, F. L., Montgomery, G. W., Morris, A. D., Morris, A. P., Murray, J. C., Nelis, M., Ohlsson, C., Oldehinkel, A. J., Ong, K. K., Ouwehand, W. H., Pasterkamp, G., Peters, A., Pramstaller, P. P., Price, J. F., Qi, L., Raitakari, O. T., Rankinen, T., Rao, D. C., Rice, T. K., Ritchie, M., Rudan, I., Salomaa, V., Samani, N. J., Saramies, J., Sarzynski, M. A., Schwarz, P. E. H., Sebert, S., Sever, P., Shuldiner, A. R., Sinisalo, J., Steinthorsdottir, V., Stolk, R. P., Tardif, J.-C., Tönjes, A., Tremblay, A., Tremoli, E., Virtamo, J., Vohl, M.-C., Amouyel, P., Asselbergs, F. W., Assimes, T. L., Bochud, M., Boehm, B. O., Boerwinkle, E., Bottinger, E. P., Bouchard, C., Cauchi, S., Chambers, J. C., Chanock, S. J., Cooper, R. S., de Bakker, P. I. W., Dedoussis, G., Ferrucci, L., Franks, P. W., Froguel, P., Groop, L. C., Haiman, C. A., Hamsten, A., Hayes, M. G., Hui, J., Hunter, D. J., Hveem, K., Jukema, J. W., Kaplan, R. C., Kivimaki, M., Kuh, D., Laakso, M., Liu, Y., Martin, N. G., März, W., Melbye, M., Moebus, S., Munroe, P. B., Njølstad, I., Oostra, B. A., Palmer, C. N. A., Pedersen, N. L., Perola, M., Pérusse, L., Peters, U., Powell, J. E., Power, C., Quertermous, T., Rauramaa, R., Reinmaa, E., Ridker, P. M., Rivadeneira, F., Rotter, J. I., Saaristo, T. E., Saleheen, D., Schlessinger, D., Slagboom, P. E., Snieder, H., Spector, T. D., Strauch, K., Stumvoll, M., Tuomilehto, J., Uusitupa, M., van der Harst, P., Völzke, H., Walker, M., Wareham, N. J., Watkins, H., Wichmann, H.-E., Wilson, J. F., Zanen, P., Deloukas, P., Heid, I. M., Lindgren, C. M., Mohlke, K. L., Speliotes, E. K., Thorsteinsdottir, U., Barroso, I., Fox, C. S., North, K. E., Strachan, D. P., Beckmann, J. S., Berndt, S. I., Boehnke, M., Borecki, I. B., McCarthy, M. I., Metspalu, A., Stefansson, K., Uitterlinden, A. G., van Duijn, C. M., Franke, L., Willer, C. J., Price, A. L., Lettre, G., Loos, R. J. F., Weedon, M. N., Ingelsson, E., O'Connell, J. R., Abecasis, G. R., Chasman, D. I., Goddard, M. E., Visscher, P. M., Hirschhorn, J. N., and Frayling, T. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Mental Health and Wellbeing
Journal Name:Nature Genetics
Publisher:Nature Publishing Group
ISSN:1061-4036
ISSN (Online):1546-1718

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