TY - JOUR
T1 - Defining the role of common variation in the genomic and biological architecture of adult human height
AU - Wood, Andrew R.
AU - Esko, Tonu
AU - Yang, Jian
AU - Vedantam, Sailaja
AU - Pers, Tune H.
AU - Gustafsson, Stefan
AU - Chun, Audrey Y.
AU - Estrada, Karol
AU - Luan, Jian'an
AU - Kutalik, Zoltan
AU - Amin, Najaf
AU - Buchkovich, Martin L.
AU - Croteau-Chonka, Damien C.
AU - Day, Felix R.
AU - Duan, Yanan
AU - Fall, Tove
AU - Fehrmann, Rudolf
AU - Ferreira, Teresa
AU - Jackson, Anne U.
AU - Karjalainen, Juha
AU - Lo, Ken Sin
AU - Locke, Adam E.
AU - Maegi, Reedik
AU - Mihailov, Evelin
AU - Porcu, Eleonora
AU - Randall, Joshua C.
AU - Scherag, Andre
AU - Vinkhuyzen, Anna A. E.
AU - Westra, Harm-Jan
AU - Mateo Leach, Irene
AU - van der Laan, Sander W.
AU - Van Vliet-Ostaptchouk, Jana V.
AU - Bruinenberg, Marcel
AU - Hartman, Catharina A.
AU - Hillege, Hans L.
AU - Nolte, Ilja M.
AU - Scholtens, Salome
AU - Smolonska, Joanna
AU - Swertz, Morris A.
AU - Verweij, Niek
AU - Vonk, Judith M.
AU - Bakker, Stephan J. L.
AU - Gansevoort, Ron T.
AU - Kumari, Meena
AU - Oldehinkel, Albertine J.
AU - Stolk, Ronald P.
AU - Asselbergs, Folkert W.
AU - Snieder, Harold
AU - van der Harst, Pim
AU - Franke, Lude
AU - Elect Med Records & Genom eMERGE C
AU - MIGen Consortium
AU - PAGE Consortium
AU - Lifelines Cohort Study
PY - 2014/11
Y1 - 2014/11
N2 - 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 similar to 2,000, similar to 3,700 and similar to 9,500 SNPs explained similar to 21%, similar to 24% and similar to 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.
AB - 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 similar to 2,000, similar to 3,700 and similar to 9,500 SNPs explained similar to 21%, similar to 24% and similar to 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.
KW - GENETIC-VARIATION
KW - COMPLEX TRAITS
KW - HERITABILITY
KW - MUTATIONS
KW - SNPS
U2 - 10.1038/ng.3097
DO - 10.1038/ng.3097
M3 - Article
C2 - 25282103
VL - 46
SP - 1173
EP - 1186
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 11
ER -