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

6533b851fe1ef96bd12a8ebb

RESEARCH PRODUCT

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

Ar Wood T Esko J Yang S Vedantam Th Pers S Gustafsson Ay Chu K Estrada J Luan Z Kutalik N Amin Ml Buchkovich Croteau Chonka Dc Fr Day Y Duan T Fall R Fehrmann T Ferreira Au Jackson J Karjalainen Ks Lo Ae Locke R Mägi E Mihailov E Porcu Jc Randall A Scherag Aa Vinkhuyzen Hj Westra Tw Winkler T Workalemahu Jh Zhao D Absher E Albrecht D Anderson J Baron M Beekman A Demirkan Gb Ehret B Feenstra Mf Feitosa K Fischer Rm Fraser A Goel J Gong Ae Justice S Kanoni Me Kleber K Kristiansson U Lim V Lotay Jc Lui M Mangino I Mateo Leach C Medina Gomez Ma Nalls Dr Nyholt Cd Palmer D Pasko S Pechlivanis I Prokopenko Js Ried S Ripke D Shungin A Stancáková Rj Strawbridge Yj Sung T Tanaka A Teumer S Trompet Van Der Laan Sw J Van Setten Van Vliet Ostaptchouk Jv Z Wang L Yengo W Zhang U Afzal J Arnlöv Gm Arscott S Bandinelli A Barrett C Bellis Aj Bennett C Berne M Blüher Jl Bolton Y Böttcher Ha Boyd M Bruinenberg Bm Buckley S Buyske Ih Caspersen Ps Chines R Clarke S Claudi Boehm M Cooper Ew Daw De Jong Pa J Deelen G Delgado Jc Denny R Dhonukshe Rutten M Dimitriou As Doney M Dörr N Eklund E Eury L Folkersen Me Garcia F Geller V Giedraitis As Go H Grallert Tb Grammer J Gräßler H Grönberg De Groot Lc Cj Groves J Haessler P Hall T Haller G Hallmans A Hannemann Ca Hartman M Hassinen C Hayward Heard Costa Nl Q Helmer G Hemani Ak Henders Hl Hillege Ma Hlatky W Hoffmann P Hoffmann O Holmen Houwing Duistermaat Jj T Illig A Isaacs Al James J Jeff B Johansen Å Johansson J Jolley T Juliusdottir J Junttila An Kho L Kinnunen N Klopp T Kocher W Kratzer P Lichtner L Lind J Lindström S Lobbens M Lorentzon Y Lu V Lyssenko Pk Magnusson A Mahajan M Maillard Wl Mcardle Ca Mckenzie S Mclachlan Pj Mclaren C Menni S Merger L Milani A Moayyeri Kl Monda Ma Morken G Müller M Müller Nurasyid Aw Musk N Narisu M Nauck Im Nolte Mm Nöthen L Oozageer S Pilz Nw Rayner F Renstrom Nr Robertson Lm Rose R Roussel S Sanna H Scharnagl S Scholtens Fr Schumacher H Schunkert Ra Scott J Sehmi T Seufferlein J Shi K Silventoinen Jh Smit Av Smith J Smolonska Av Stanton K Stirrups Dj Stott Hm Stringham J Sundström Ma Swertz Ac Syvänen Bo Tayo G Thorleifsson Jp Tyrer S Van Dijk Van Schoor Nm N Van Der Velde D Van Heemst Van Oort Fv Sh Vermeulen N Verweij Jm Vonk Ll Waite M Waldenberger R Wennauer Lr Wilkens C Willenborg T Wilsgaard Mk Wojczynski A Wong Af Wright Q Zhang D Arveiler Sj Bakker J Beilby Rn Bergman S Bergmann R Biffar J Blangero Di Boomsma Sr Bornstein P Bovet P Brambilla Mj Brown H Campbell Mj Caulfield A Chakravarti R Collins Fs Collins Dc Crawford La Cupples J Danesh U De Faire Den Ruijter Hm R Erbel J Erdmann Jg Eriksson M Farrall Eleuterio Ferrannini J Ferrières I Ford Ng Forouhi T Forrester Rt Gansevoort Pv Gejman C Gieger A Golay O Gottesman V Gudnason U Gyllensten Dw Haas As Hall Tb Harris At Hattersley Ac Heath C Hengstenberg Aa Hicks La Hindorff Ad Hingorani A Hofman Gk Hovingh Se Humphries Sc Hunt E Hypponen Kb Jacobs Mr Jarvelin P Jousilahti Am Jula J Kaprio Jj Kastelein M Kayser F Kee Keinanen Kiukaanniemi Sm La Kiemeney Js Kooner C Kooperberg S Koskinen P Kovacs At Kraja M Kumari J Kuusisto Ta Lakka C Langenberg L Le Marchand T Lehtimäki S Lupoli Pa Madden S Männistö P Manunta A Marette Tc Matise B Mcknight T Meitinger Fl Moll Gw Montgomery Ad Morris Ap Morris Jc Murray M Nelis C Ohlsson Aj Oldehinkel Kk Ong Wh Ouwehand G Pasterkamp A Peters Pp Pramstaller Jf Price L Qi Ot Raitakari T Rankinen Dc Rao Tk Rice M Ritchie I Rudan V Salomaa Nj Samani J Saramies Ma Sarzynski Pe Schwarz S Sebert P Sever Ar Shuldiner J Sinisalo V Steinthorsdottir Rp Stolk Jc Tardif A Tönjes A Tremblay E Tremoli J Virtamo Mc Vohl Electronic Medical Records Consortium Genomics Consortium Migen Consortium Pagege Lifelines Cohort Study P Amouyel Fw Asselbergs Tl Assimes M Bochud Bo Boehm E Boerwinkle Ep Bottinger C Bouchard S Cauchi Jc Chambers Sj Chanock Rs Cooper De Bakker Pi G Dedoussis L Ferrucci Pw Franks P Froguel Lc Groop Ca Haiman A Hamsten Mg Hayes J Hui Dj Hunter K Hveem Jw Jukema Rc Kaplan M Kivimaki D Kuh M Laakso Y Liu Ng Martin W März M Melbye S Moebus Pb Munroe I Njølstad Ba Oostra Cn Palmer Nl Pedersen M Perola L Pérusse U Peters Je Powell C Power T Quertermous R Rauramaa E Reinmaa Pm Ridker F Rivadeneira Ji Rotter Te Saaristo D Saleheen D Schlessinger Pe Slagboom H Snieder Td Spector K Strauch M Stumvoll J Tuomilehto M Uusitupa P Van Der Harst H Völzke M Walker Nj Wareham H Watkins He Wichmann Jf Wilson P Zanen P Deloukas Im Heid Cm Lindgren Kl Mohlke Ek Speliotes U Thorsteinsdottir I Barroso Cs Fox Ke North Dp Strachan Js Beckmann Si Berndt M Boehnke Ib Borecki Mi Mccarthy A Metspalu K Stefansson Ag Uitterlinden Van Duijn Cm L Franke Cj Willer Al Price G Lettre Rj Loos Mn Weedon E Ingelsson Jr O'connell Gr Abecasis Di Chasman Me Goddard Pm Visscher Jn Hirschhorn T. M. Frayling

subject

Netherlands Twin Register (NTR)BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA Electronic Medical Records and Genomics (eMEMERGEGE) Consortium Medizin Genome-wide association study 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 heritability 0302 clinical medicine Genome-wide European Continental Ancestry Group/genetics SNPS Oligonucleotide Array Sequence Analysis snps Genetics & Heredity ddc:616 Genetics Medical And Health Sciences 0303 health sciences education.field_of_study variants Body Height/genetics GENETIC-VARIATION Biological Sciences Polymorphism Single Nucleotide/genetics Genetic Variation/genetics Urological cancers Radboud Institute for Health Sciences [Radboudumc 15]Genome-Wide Association Study/methods body height genetic-variation Life Sciences & Biomedicine Single Nucleotide/genetics Human Adult European Continental Ancestry Group Population Population Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Article White People NO complex traits 03 medical and health sciences Genetic variation heritability adult height /dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_Genetics Humans Polymorphism Human height PAGEGE Consortium education Gene VLAG 030304 developmental biology Global Nutrition Wereldvoeding Analysis of Variance Genome-wide; heritability; variants genome-wide association study Science & Technology Whites Oligonucleotide Array Sequence Analysi MUTATIONS COMPLEX TRAITS ta1184 Klinisk medicin population genetics Genetic Variation Heritability ta3121 mutations Genetic architecture Body Height Genetics Population genetic variation MIGen Consortium Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5]Clinical Medicine 030217 neurology & neurosurgery height LifeLines Cohort Study Developmental Biology Genome-Wide Association Study

description

Item does not contain fulltext 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.

year	journal	country	edition	language
2014-11-01	Nature genetics

10.1038/ng.3097 https://doi.org/10.1038/ng.3097