Hundreds of variants clustered in genomic loci and biological pathways affect human height.
Lango Allen H., Estrada K., Lettre G., Berndt SI., Weedon MN., Rivadeneira F., Willer CJ., Jackson AU., Vedantam S., Raychaudhuri S., Ferreira T., Wood AR., Weyant RJ., Segrè AV., Speliotes EK., Wheeler E., Soranzo N., Park J-H., Yang J., Gudbjartsson D., Heard-Costa NL., Randall JC., Qi L., Vernon Smith A., Mägi R., Pastinen T., Liang L., Heid IM., Luan J., Thorleifsson G., Winkler TW., Goddard ME., Sin Lo K., Palmer C., Workalemahu T., Aulchenko YS., Johansson A., Zillikens MC., Feitosa MF., Esko T., Johnson T., Ketkar S., Kraft P., Mangino M., Prokopenko I., Absher D., Albrecht E., Ernst F., Glazer NL., Hayward C., Hottenga J-J., Jacobs KB., Knowles JW., Kutalik Z., Monda KL., Polasek O., Preuss M., Rayner NW., Robertson NR., Steinthorsdottir V., Tyrer JP., Voight BF., Wiklund F., Xu J., Zhao JH., Nyholt DR., Pellikka N., Perola M., Perry JRB., Surakka I., Tammesoo M-L., Altmaier EL., Amin N., Aspelund T., Bhangale T., Boucher G., Chasman DI., Chen C., Coin L., Cooper MN., Dixon AL., Gibson Q., Grundberg E., Hao K., Juhani Junttila M., Kaplan LM., Kettunen J., König IR., Kwan T., Lawrence RW., Levinson DF., Lorentzon M., McKnight B., Morris AP., Müller M., Suh Ngwa J., Purcell S., Rafelt S., Salem RM., Salvi E., Sanna S., Shi J., Sovio U., Thompson JR., Turchin MC., Vandenput L., Verlaan DJ., Vitart V., White CC., Ziegler A., Almgren P., Balmforth AJ., Campbell H., Citterio L., De Grandi A., Dominiczak A., Duan J., Elliott P., Elosua R., Eriksson JG., Freimer NB., Geus EJC., Glorioso N., Haiqing S., Hartikainen A-L., Havulinna AS., Hicks AA., Hui J., Igl W., Illig T., Jula A., Kajantie E., Kilpeläinen TO., Koiranen M., Kolcic I., Koskinen S., Kovacs P., Laitinen J., Liu J., Lokki M-L., Marusic A., Maschio A., Meitinger T., Mulas A., Paré G., Parker AN., Peden JF., Petersmann A., Pichler I., Pietiläinen KH., Pouta A., Ridderstråle M., Rotter JI., Sambrook JG., Sanders AR., Schmidt CO., Sinisalo J., Smit JH., Stringham HM., Bragi Walters G., Widen E., Wild SH., Willemsen G., Zagato L., Zgaga L., Zitting P., Alavere H., Farrall M., McArdle WL., Nelis M., Peters MJ., Ripatti S., van Meurs JBJ., Aben KK., Ardlie KG., Beckmann JS., Beilby JP., Bergman RN., Bergmann S., Collins FS., Cusi D., den Heijer M., Eiriksdottir G., Gejman PV., Hall AS., Hamsten A., Huikuri HV., Iribarren C., Kähönen M., Kaprio J., Kathiresan S., Kiemeney L., Kocher T., Launer LJ., Lehtimäki T., Melander O., Mosley TH., Musk AW., Nieminen MS., O'Donnell CJ., Ohlsson C., Oostra B., Palmer LJ., Raitakari O., Ridker PM., Rioux JD., Rissanen A., Rivolta C., Schunkert H., Shuldiner AR., Siscovick DS., Stumvoll M., Tönjes A., Tuomilehto J., van Ommen G-J., Viikari J., Heath AC., Martin NG., Montgomery GW., Province MA., Kayser M., Arnold AM., Atwood LD., Boerwinkle E., Chanock SJ., Deloukas P., Gieger C., Grönberg H., Hall P., Hattersley AT., Hengstenberg C., Hoffman W., Lathrop GM., Salomaa V., Schreiber S., Uda M., Waterworth D., Wright AF., Assimes TL., Barroso I., Hofman A., Mohlke KL., Boomsma DI., Caulfield MJ., Cupples LA., Erdmann J., Fox CS., Gudnason V., Gyllensten U., Harris TB., Hayes RB., Jarvelin M-R., Mooser V., Munroe PB., Ouwehand WH., Penninx BW., Pramstaller PP., Quertermous T., Rudan I., Samani NJ., Spector TD., Völzke H., Watkins H., Wilson JF., Groop LC., Haritunians T., Hu FB., Kaplan RC., Metspalu A., North KE., Schlessinger D., Wareham NJ., Hunter DJ., O'Connell JR., Strachan DP., Wichmann H-E., Borecki IB., van Duijn CM., Schadt EE., Thorsteinsdottir U., Peltonen L., Uitterlinden AG., Visscher PM., Chatterjee N., Loos RJF., Boehnke M., McCarthy MI., Ingelsson E., Lindgren CM., Abecasis GR., Stefansson K., Frayling TM., Hirschhorn JN.
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