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Hundreds of variants clustered in genomic loci and biological pathways affect human height.

ABSTRACT: Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P?

SUBMITTER: Lango Allen H

PROVIDER: S-EPMC2955183 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Hundreds of variants clustered in genomic loci and biological pathways affect human height.

Lango Allen Hana H Estrada Karol K Lettre Guillaume G Berndt Sonja I SI Weedon Michael N MN Rivadeneira Fernando F Willer Cristen J CJ Jackson Anne U AU Vedantam Sailaja S Raychaudhuri Soumya S Ferreira Teresa T Wood Andrew R AR Weyant Robert J RJ Segrè Ayellet V AV Speliotes Elizabeth K EK Wheeler Eleanor E Soranzo Nicole N Park Ju-Hyun JH Yang Jian J Gudbjartsson Daniel D Heard-Costa Nancy L NL Randall Joshua C JC Qi Lu L Vernon Smith Albert A Mägi Reedik R Pastinen Tomi T Liang Liming L Heid Iris M IM Luan Jian'an J Thorleifsson Gudmar G Winkler Thomas W TW Goddard Michael E ME Sin Lo Ken K Palmer Cameron C Workalemahu Tsegaselassie T Aulchenko Yurii S YS Johansson Asa A Zillikens M Carola MC Feitosa Mary F MF Esko Tõnu T Johnson Toby T Ketkar Shamika S Kraft Peter P Mangino Massimo M Prokopenko Inga I Absher Devin D Albrecht Eva E Ernst Florian F Glazer Nicole L NL Hayward Caroline C Hottenga Jouke-Jan JJ Jacobs Kevin B KB Knowles Joshua W JW Kutalik Zoltán Z Monda Keri L KL Polasek Ozren O Preuss Michael M Rayner Nigel W NW Robertson Neil R NR Steinthorsdottir Valgerdur V Tyrer Jonathan P JP Voight Benjamin F BF Wiklund Fredrik F Xu Jianfeng J Zhao Jing Hua JH Nyholt Dale R DR Pellikka Niina N Perola Markus M Perry John R B JR Surakka Ida I Tammesoo Mari-Liis ML Altmaier Elizabeth L EL Amin Najaf N Aspelund Thor T Bhangale Tushar T Boucher Gabrielle G Chasman Daniel I DI Chen Constance C Coin Lachlan L Cooper Matthew N MN Dixon Anna L AL Gibson Quince Q Grundberg Elin E Hao Ke K Juhani Junttila M M Kaplan Lee M LM Kettunen Johannes J König Inke R IR Kwan Tony T Lawrence Robert W RW Levinson Douglas F DF Lorentzon Mattias M McKnight Barbara B Morris Andrew P AP Müller Martina M Suh Ngwa Julius J Purcell Shaun S Rafelt Suzanne S Salem Rany M RM Salvi Erika E Sanna Serena S Shi Jianxin J Sovio Ulla U Thompson John R JR Turchin Michael C MC Vandenput Liesbeth L Verlaan Dominique J DJ Vitart Veronique V White Charles C CC Ziegler Andreas A Almgren Peter P Balmforth Anthony J AJ Campbell Harry H Citterio Lorena L De Grandi Alessandro A Dominiczak Anna A Duan Jubao J Elliott Paul P Elosua Roberto R Eriksson Johan G JG Freimer Nelson B NB Geus Eco J C EJ Glorioso Nicola N Haiqing Shen S Hartikainen Anna-Liisa AL Havulinna Aki S AS Hicks Andrew A AA Hui Jennie J Igl Wilmar W Illig Thomas T Jula Antti A Kajantie Eero E Kilpeläinen Tuomas O TO Koiranen Markku M Kolcic Ivana I Koskinen Seppo S Kovacs Peter P Laitinen Jaana J Liu Jianjun J Lokki Marja-Liisa ML Marusic Ana A Maschio Andrea A Meitinger Thomas T Mulas Antonella A Paré Guillaume G Parker Alex N AN Peden John F JF Petersmann Astrid A Pichler Irene I Pietiläinen Kirsi H KH Pouta Anneli A Ridderstråle Martin M Rotter Jerome I JI Sambrook Jennifer G JG Sanders Alan R AR Schmidt Carsten Oliver CO Sinisalo Juha J Smit Jan H JH Stringham Heather M HM Bragi Walters G G Widen Elisabeth E Wild Sarah H SH Willemsen Gonneke G Zagato Laura L Zgaga Lina L Zitting Paavo P Alavere Helene H Farrall Martin M McArdle Wendy L WL Nelis Mari M Peters Marjolein J MJ Ripatti Samuli S van Meurs Joyce B J JB Aben Katja K KK Ardlie Kristin G KG Beckmann Jacques S JS Beilby John P JP Bergman Richard N RN Bergmann Sven S Collins Francis S FS Cusi Daniele D den Heijer Martin M Eiriksdottir Gudny G Gejman Pablo V PV Hall Alistair S AS Hamsten Anders A Huikuri Heikki V HV Iribarren Carlos C Kähönen Mika M Kaprio Jaakko J Kathiresan Sekar S Kiemeney Lambertus L Kocher Thomas T Launer Lenore J LJ Lehtimäki Terho T Melander Olle O Mosley Tom H TH Musk Arthur W AW Nieminen Markku S MS O'Donnell Christopher J CJ Ohlsson Claes C Oostra Ben B Palmer Lyle J LJ Raitakari Olli O Ridker Paul M PM Rioux John D JD Rissanen Aila A Rivolta Carlo C Schunkert Heribert H Shuldiner Alan R AR Siscovick David S DS Stumvoll Michael M Tönjes Anke A Tuomilehto Jaakko J van Ommen Gert-Jan GJ Viikari Jorma J Heath Andrew C AC Martin Nicholas G NG Montgomery Grant W GW Province Michael A MA Kayser Manfred M Arnold Alice M AM Atwood Larry D LD Boerwinkle Eric E Chanock Stephen J SJ Deloukas Panos P Gieger Christian C Grönberg Henrik H Hall Per P Hattersley Andrew T AT Hengstenberg Christian C Hoffman Wolfgang W Lathrop G Mark GM Salomaa Veikko V Schreiber Stefan S Uda Manuela M Waterworth Dawn D Wright Alan F AF Assimes Themistocles L TL Barroso Inês I Hofman Albert A Mohlke Karen L KL Boomsma Dorret I DI Caulfield Mark J MJ Cupples L Adrienne LA Erdmann Jeanette J Fox Caroline S CS Gudnason Vilmundur V Gyllensten Ulf U Harris Tamara B TB Hayes Richard B RB Jarvelin Marjo-Riitta MR Mooser Vincent V Munroe Patricia B PB Ouwehand Willem H WH Penninx Brenda W BW Pramstaller Peter P PP Quertermous Thomas T Rudan Igor I Samani Nilesh J NJ Spector Timothy D TD Völzke Henry H Watkins Hugh H Wilson James F JF Groop Leif C LC Haritunians Talin T Hu Frank B FB Kaplan Robert C RC Metspalu Andres A North Kari E KE Schlessinger David D Wareham Nicholas J NJ Hunter David J DJ O'Connell Jeffrey R JR Strachan David P DP Wichmann H-Erich HE Borecki Ingrid B IB van Duijn Cornelia M CM Schadt Eric E EE Thorsteinsdottir Unnur U Peltonen Leena L Uitterlinden André G AG Visscher Peter M PM Chatterjee Nilanjan N Loos Ruth J F RJ Boehnke Michael M McCarthy Mark I MI Ingelsson Erik E Lindgren Cecilia M CM Abecasis Gonçalo R GR Stefansson Kari K Frayling Timothy M TM Hirschhorn Joel N JN

Nature 20100929 7317

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a h ...[more]

PMID: 20881960

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Hundreds of variants clustered in genomic loci and biological pathways affect human height.

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Hundreds of variants clustered in genomic loci and biological pathways affect human height.

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