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

明确常见变异在成人身高基因组和生物学结构中的作用

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作者：Wood,Andrew R,Esko,Tonu,Yang,Jian,Vedantam,Sailaja,Pers,Tune H,Gustafsson,Stefan,Chu,Audrey Y,Estrada,Karol,Luan,Jian'an,Kutalik,Zoltán,Amin,Najaf,Buchkovich,Martin L,Croteau-Chonka,Damien C,Day,Felix R,Duan,Yanan,Fall,Tove,Fehrmann,Rudolf,Ferreira,Teresa,Jackson,Anne U,Karjalainen,Juha,Lo,Ken Sin,Locke,Adam E,Mägi,Reedik,Mihailov,Evelin,Porcu,Eleonora,Randall,Joshua C,Scherag,André,Vinkhuyzen,Anna A E,Westra,Harm-Jan,Winkler,Thomas W,Workalemahu,Tsegaselassie,Zhao,Jing Hua,Absher,Devin,Albrecht,Eva,Anderson,Denise,Baron,Jeffrey,Beekman,Marian,Demirkan,Ayse,Ehret,Georg B,Feenstra,Bjarke,Feitosa,Mary F,Fischer,Krista,Fraser,Ross M,Goel,Anuj,Gong,Jian,Justice,Anne E,Kanoni,Stavroula,Kleber,Marcus E,Kristiansson,Kati,Lim,Unhee,Lotay,Vaneet,Lui,Julian C,Mangino,Massimo,Mateo Leach,Irene,Medina-Gomez,Carolina,Nalls,Michael A,Nyholt,Dale R,Palmer,Cameron D,Pasko,Dorota,Pechlivanis,Sonali,Prokopenko,Inga,Ried,Janina S,Ripke,Stephan,Shungin,Dmitry,Stancáková,Alena,Strawbridge,Rona J,Sung,Yun Ju,Tanaka,Toshiko,Teumer,Alexander,Trompet,Stella,van der Laan,Sander W,van Setten,Jessica,Van Vliet-Ostaptchouk,Jana V,Wang,Zhaoming,Yengo,Loïc,Zhang,Weihua,Afzal,Uzma,Arnlöv,Johan,Arscott,Gillian M,Bandinelli,Stefania,Barrett,Amy,Bellis,Claire,Bennett,Amanda J,Berne,Christian,Blüher,Matthias,Bolton,Jennifer L,Böttcher,Yvonne,Boyd,Heather A,Bruinenberg,Marcel,Buckley,Brendan M,Buyske,Steven,Caspersen,Ida H,Chines,Peter S,Clarke,Robert,Claudi-Boehm,Simone,Cooper,Matthew,Daw,E Warwick,De Jong,Pim A,Deelen,Joris,Delgado,Graciela,Denny,Josh C,Dhonukshe-Rutten,Rosalie,Dimitriou,Maria,Doney,Alex S F,Dörr,Marcus,Eklund,Niina,Eury,Elodie,Folkersen,Lasse,Garcia,Melissa E,Geller,Frank,Giedraitis,Vilmantas,Go,Alan S,Grallert,Harald,Grammer,Tanja B,Gräßler,Jürgen,Grönberg,Henrik,de Groot,Lisette C P G M,Groves,Christopher J,Haessler,Jeffrey,Hall,Per,Haller,Toomas,Hallmans,Goran,Hannemann,Anke,Hartman,Catharina A,Hassinen,Maija,Hayward,Caroline,Heard-Costa,Nancy L,Helmer,Quinta,Hemani,Gibran,Henders,Anjali K,Hillege,Hans L,Hlatky,Mark A,Hoffmann,Wolfgang,Hoffmann,Per,Holmen,Oddgeir,Houwing-Duistermaat,Jeanine J,Illig,Thomas,Isaacs,Aaron,James,Alan L,Jeff,Janina,Johansen,Berit,Johansson,Åsa,Jolley,Jennifer,Juliusdottir,Thorhildur,Junttila,Juhani,Kho,Abel N,Kinnunen,Leena,Klopp,Norman,Kocher,Thomas,Kratzer,Wolfgang,Lichtner,Peter,Lind,Lars,Lindström,Jaana,Lobbens,Stéphane,Lorentzon,Mattias,Lu,Yingchang,Lyssenko,Valeriya,Magnusson,Patrik K E,Mahajan,Anubha,Maillard,Marc,McArdle,Wendy L,McKenzie,Colin A,McLachlan,Stela,McLaren,Paul J,Menni,Cristina,Merger,Sigrun,Milani,Lili,Moayyeri,Alireza,Monda,Keri L,Morken,Mario A,Müller,Gabriele,Müller-Nurasyid,Martina,Musk,Arthur W,Narisu,Narisu,Nauck,Matthias,Nolte,Ilja M,Nöthen,Markus M,Oozageer,Laticia,Pilz,Stefan,Rayner,Nigel W,Renstrom,Frida,Robertson,Neil R,Rose,Lynda M,Roussel,Ronan,Sanna,Serena,Scharnagl,Hubert,Scholtens,Salome,Schumacher,Fredrick R,Schunkert,Heribert,Scott,Robert A,Sehmi,Joban,Seufferlein,Thomas,Shi,Jianxin,Silventoinen,Karri,Smit,Johannes H,Smith,Albert Vernon,Smolonska,Joanna,Stanton,Alice V,Stirrups,Kathleen,Stott,David J,Stringham,Heather M,Sundström,Johan,Swertz,Morris A,Syvänen,Ann-Christine,Tayo,Bamidele O,Thorleifsson,Gudmar,Tyrer,Jonathan P,van Dijk,Suzanne,van Schoor,Natasja M,van der Velde,Nathalie,van Heemst,Diana,van Oort,Floor V A,Vermeulen,Sita H,Verweij,Niek,Vonk,Judith M,Waite,Lindsay L,Waldenberger,Melanie,Wennauer,Roman,Wilkens,Lynne R,Willenborg,Christina,Wilsgaard,Tom,Wojczynski,Mary K,Wong,Andrew,Wright,Alan F,Zhang,Qunyuan,Arveiler,Dominique,Bakker,Stephan J L,Beilby,John,Bergman,Richard N,Bergmann,Sven,Biffar,Reiner,Blangero,John,Boomsma,Dorret I,Bornstein,Stefan R,Bovet,Pascal,Brambilla,Paolo,Brown,Morris J,Campbell,Harry,Caulfield,Mark J,Chakravarti,Aravinda,Collins,Rory,Collins,Francis S,Crawford,Dana C,Cupples,L Adrienne,Danesh,John,de Faire,Ulf,den Ruijter,Hester M,Erbel,Raimund,Erdmann,Jeanette,Eriksson,Johan G,Farrall,Martin,Ferrannini,Ele,Ferrières,Jean,Ford,Ian,Forouhi,Nita G,Forrester,Terrence,Gansevoort,Ron T,Gejman,Pablo V,Gieger,Christian,Golay,Alain,Gottesman,Omri,Gudnason,Vilmundur,Gyllensten,Ulf,Haas,David W,Hall,Alistair S,Harris,Tamara B,Hattersley,Andrew T,Heath,Andrew C,Hengstenberg,Christian,Hicks,Andrew A,Hindorff,Lucia A,Hingorani,Aroon D,Hofman,Albert,Hovingh,G Kees,Humphries,Steve E,Hunt,Steven C,Hypponen,Elina,Jacobs,Kevin B,Jarvelin,Marjo-Riitta,Jousilahti,Pekka,Jula,Antti M,Kaprio,Jaakko,Kastelein,John J P,Kayser,Manfred,Kee,Frank,Keinanen-Kiukaanniemi,Sirkka M,Kiemeney,Lambertus A,Kooner,Jaspal S,Kooperberg,Charles,Koskinen,Seppo,Kovacs,Peter,Kraja,Aldi T,Kumari,Meena,Kuusisto,Johanna,Lakka,Timo A,Langenberg,Claudia,Le Marchand,Loic,Lehtimäki,Terho,Lupoli,Sara,Madden,Pamela A F,Männistö,Satu,Manunta,Paolo,Marette,André,Matise,Tara C,McKnight,Barbara,Meitinger,Thomas,Moll,Frans L,Montgomery,Grant W,Morris,Andrew D,Morris,Andrew P,Murray,Jeffrey C,Nelis,Mari,Ohlsson,Claes,Oldehinkel,Albertine J,Ong,Ken K,Ouwehand,Willem H,Pasterkamp,Gerard,Peters,Annette,Pramstaller,Peter P,Price,Jackie F,Qi,Lu,Raitakari,Olli T,Rankinen,Tuomo,Rao,D C,Rice,Treva K,Ritchie,Marylyn,Rudan,Igor,Salomaa,Veikko,Samani,Nilesh J,Saramies,Jouko,Sarzynski,Mark A,Schwarz,Peter E H,Sebert,Sylvain,Sever,Peter,Shuldiner,Alan R,Sinisalo,Juha,Steinthorsdottir,Valgerdur,Stolk,Ronald P,Tardif,Jean-Claude,Tönjes,Anke,Tremblay,Angelo,Tremoli,Elena,Virtamo,Jarmo,Vohl,Marie-Claude,Amouyel,Philippe,Asselbergs,Folkert W,Assimes,Themistocles L,Bochud,Murielle,Boehm,Bernhard O,Boerwinkle,Eric,Bottinger,Erwin P,Bouchard,Claude,Cauchi,Stéphane,Chambers,John C,Chanock,Stephen J,Cooper,Richard S,de Bakker,Paul I W,Dedoussis,George,Ferrucci,Luigi,Franks,Paul W,Froguel,Philippe,Groop,Leif C,Haiman,Christopher A,Hamsten,Anders,Hayes,M Geoffrey,Hui,Jennie,Hunter,David J,Hveem,Kristian,Jukema,J Wouter,Kaplan,Robert C,Kivimaki,Mika,Kuh,Diana,Laakso,Markku,Liu,Yongmei,Martin,Nicholas G,März,Winfried,Melbye,Mads,Moebus,Susanne,Munroe,Patricia B,Njølstad,Inger,Oostra,Ben A,Palmer,Colin N A,Pedersen,Nancy L,Perola,Markus,Pérusse,Louis,Peters,Ulrike,Powell,Joseph E,Power,Chris,Quertermous,Thomas,Rauramaa,Rainer,Reinmaa,Eva,Ridker,Paul M,Rivadeneira,Fernando,Rotter,Jerome I,Saaristo,Timo E,Saleheen,Danish,Schlessinger,David,Slagboom,P Eline,Snieder,Harold,Spector,Tim D,Strauch,Konstantin,Stumvoll,Michael,Tuomilehto,Jaakko,Uusitupa,Matti,van der Harst,Pim,Völzke,Henry,Walker,Mark,Wareham,Nicholas J,Watkins,Hugh,Wichmann,H-Erich,Wilson,James F,Zanen,Pieter,Deloukas,Panos,Heid,Iris M,Lindgren,Cecilia M,Mohlke,Karen L,Speliotes,Elizabeth K,Thorsteinsdottir,Unnur,Barroso,Inês,Fox,Caroline S,North,Kari E,Strachan,David P,Beckmann,Jacques S,Berndt,Sonja I,Boehnke,Michael,Borecki,Ingrid B,McCarthy,Mark I,Metspalu,Andres,Stefansson,Kari,Uitterlinden,André G,van Duijn,Cornelia M,Franke,Lude,Willer,Cristen J,Price,Alkes L,Lettre,Guillaume,Loos,Ruth J F,Weedon,Michael N,Ingelsson,Erik,O'Connell,Jeffrey R,Abecasis,Goncalo R,Chasman,Daniel I,Goddard,Michael E,Visscher,Peter M,Hirschhorn,Joel N,Frayling,Timothy M
期刊：Nature Genetics影响因子：29.000
时间：2014起止号：2014 Nov;46(11):1173-86
doi：10.1038/ng.3097

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.

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