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

Wood, A. R., Esko, T., Yang, J., Vedantam, S., Pers, T. H., Gustafsson, S., et al. (2014). Defining the role of common variation in the genomic and biological architecture of adult human height. Nat Genet, 46(11), 1173-86. doi:10.1038/ng.3097.

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Wood, A. R., Author
Esko, T., Author
Yang, J., Author
Vedantam, S., Author
Pers, T. H., Author
Gustafsson, S., Author
Chu, A. Y., Author
Estrada, K., Author
Luan, J., Author
Kutalik, Z., Author
Amin, N., Author
Buchkovich, M. L., Author
Croteau-Chonka, D. C., Author
Day, F. R., Author
Duan, Y., Author
Fall, T., Author
Fehrmann, R., Author
Ferreira, T., Author
Jackson, A. U., Author
Karjalainen, J., Author
Lo, K. S., AuthorLocke, A. E., AuthorMagi, R., AuthorMihailov, E., AuthorPorcu, E., AuthorRandall, J. C., AuthorScherag, A., AuthorVinkhuyzen, A. A., AuthorWestra, H. J., AuthorWinkler, T. W., AuthorWorkalemahu, T., AuthorZhao, J. H., AuthorAbsher, D., AuthorAlbrecht, E., AuthorAnderson, D., AuthorBaron, J., AuthorBeekman, M., AuthorDemirkan, A., AuthorEhret, G. B., AuthorFeenstra, B., AuthorFeitosa, M. F., AuthorFischer, K., AuthorFraser, R. M., AuthorGoel, A., AuthorGong, J., AuthorJustice, A. E., AuthorKanoni, S., AuthorKleber, M. E., AuthorKristiansson, K., AuthorLim, U., AuthorLotay, V., AuthorLui, J. C., AuthorMangino, M., AuthorMateo Leach, I., AuthorMedina-Gomez, C., AuthorNalls, M. A., AuthorNyholt, D. R., AuthorPalmer, C. D., AuthorPasko, D., AuthorPechlivanis, S., AuthorProkopenko, I., AuthorRied, J. S., AuthorRipke, S., AuthorShungin, D., AuthorStancakova, A., AuthorStrawbridge, R. J., AuthorSung, Y. J., AuthorTanaka, T., AuthorTeumer, A., AuthorTrompet, S., Authorvan der Laan, S. W., Authorvan Setten, J., AuthorVan Vliet-Ostaptchouk, J. V., AuthorWang, Z., AuthorYengo, L., AuthorZhang, W., AuthorAfzal, U., AuthorArnlov, J., AuthorArscott, G. M., AuthorBandinelli, S., AuthorBarrett, A., AuthorBellis, C., AuthorBennett, A. J., AuthorBerne, C., AuthorBluher, M., AuthorBolton, J. L., AuthorBottcher, Y., AuthorBoyd, H. A., AuthorBruinenberg, M., AuthorBuckley, B. M., AuthorBuyske, S., AuthorCaspersen, I. H., AuthorChines, P. S., AuthorClarke, R., AuthorClaudi-Boehm, S., AuthorCooper, M., AuthorDaw, E. W., AuthorDe Jong, P. A., AuthorDeelen, J.1, Author           Goddard, M. E., AuthorVisscher, P. M., AuthorHirschhorn, J. N., AuthorFrayling, T. M., Author more..
Affiliations:
1Deelen – Genetics and Biomarkers of Human Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_3394006              

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Free keywords: Adult Analysis of Variance Body Height/*genetics European Continental Ancestry Group/*genetics Genetic Variation/*genetics Genetics, Population Genome-Wide Association Study/methods Humans Oligonucleotide Array Sequence Analysis Polymorphism, Single Nucleotide/*genetics
 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 approximately 2,000, approximately 3,700 and approximately 9,500 SNPs explained approximately 21%, approximately 24% and approximately 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/beta-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.

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 Dates: 2014-112014-10-06
 Publication Status: Issued
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 Identifiers: Other: 25282103
DOI: 10.1038/ng.3097
ISSN: 1546-1718 (Electronic)1061-4036 (Linking)
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Title: Nat Genet
Source Genre: Journal
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Pages: - Volume / Issue: 46 (11) Sequence Number: - Start / End Page: 1173 - 86 Identifier: -