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Journal Article

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

Authors

  1. Andrew R. Wood
  2. Tonu Esko
  3. Jian Yang
  4. Sailaja Vedantam
  5. Tune H. Pers
  6. Stefan Gustafsson
  7. Audrey Y. Chu
  8. Karol Estrada
  9. Jian'an Luan
  10. Zoltán Kutalik
  11. Najaf Amin
  12. Martin L. Buchkovich
  13. Damien C. Croteau-Chonka
  14. Felix R. Day
  15. Yanan Duan
  16. Tove Fall
  17. Rudolf Fehrmann
  18. Teresa Ferreira
  19. Anne U. Jackson
  20. Juha Karjalainen
  21. Ken Sin Lo
  22. Adam E. Locke
  23. Reedik Magi
  24. Evelin Mihailov
  25. Eleonora Porcu
  26. Joshua C. Randall
  27. André Scherag
  28. Anna A.E. Vinkhuyzen
  29. Harm-Jan Westra
  30. Thomas W. Winkler
  31. Tsegaselassie Workalemahu
  32. Jing Hua Zhao
  33. Devin Absher
  34. Eva Albrecht
  35. Denise Anderson
  36. Jeffrey Baron
  37. Marian Beekman
  38. Ayse Demirkan
  39. Georg B. Ehret
  40. Bjarke Feenstra
  41. Mary F. Feitosa
  42. Krista Fischer
  43. Ross M. Fraser
  44. Anuj Goel
  45. Jian Gong
  46. Anne E. Justice
  47. Stavroula Kanoni
  48. Marcus E. Kleber
  49. Kati Kristiansson
  50. Unhee Lim
  51. Vaneet Lotay
  52. Julian C. Lui
  53. Massimo Mangino
  54. Irene Mateo Leach
  55. Carolina Medina-Gomez
  56. Michael A. Nalls
  57. Dale R. Nyholt
  58. Cameron D. Palmer
  59. Dorota Pasko
  60. Sonali Pechlivanis
  61. Inga Prokopenko
  62. Janina S. Ried
  63. Stephan Ripke
  64. Dmitry Shungin
  65. Alena Stancakova
  66. Rona J. Strawbridge
  67. Yun Ju Sung
  68. Toshiko Tanaka
  69. Alexander Teumer
  70. Stella Trompet
  71. Sander W. van der Laan
  72. Jessica van Setten
  73. Jana V. van Vliet-Ostaptchouk
  74. Zhaoming Wang
  75. Loic Yengo
  76. Weihua Zhang
  77. Uzma Afzal
  78. Johan Ärnlöv
  79. Gillian M. Arscott
  80. Stefania Bandinelli
  81. Amy Barrett
  82. Claire Bellis
  83. Amanda J. Bennett
  84. Christian Berne
  85. Matthias Bluher
  86. Jennifer L. Bolton
  87. Yvonne Bottcher
  88. Heather A. Boyd
  89. Marcel Bruinenberg
  90. Brendan M. Buckley
  91. Steven Buyske
  92. Ida H. Caspersen
  93. Peter S. Chines
  94. Robert Clarke
  95. Simone Claudi-Boehm
  96. Matthew Cooper
  97. E. Warwick Daw
  98. Pim A. de Jong
  99. Joris Deelen
  100. Graciela Delgado
  101. Josh C. Denny
  102. Rosalie Dhonukshe-Rutten
  103. Maria Dimitriou
  104. Alex S. F. Doney
  105. Marcus Dörr
  106. Niina Eklund
  107. Elodie Eury
  108. Lasse Folkersen
  109. Melissa E. Garcia
  110. Frank Geller
  111. Vilmantas Giedraitis
  112. Alan S. Go
  113. Harald Grallert
  114. Tanja B. Grammer
  115. Jurgen Graszler
  116. Henrik Gronberg
  117. Lisette C. P. G. M. de Groot
  118. Christopher J. Groves
  119. Jeffrey Haessler
  120. Per Hall
  121. Toomas Haller
  122. Goran Hallmans
  123. Anke Hannemann
  124. Catharina A. Hartman
  125. Maija Hassinen
  126. Caroline Hayward
  127. Nancy L. Heard-Costa
  128. Quinta Helmer
  129. Gibran Hemani
  130. Anjali K. Henders
  131. Hans L. Hillege
  132. Mark A. Hlatky
  133. Wolfgang Hoffmann
  134. Per Hoffmann
  135. Oddgeir Holmen
  136. Jeanine J. Houwing-Duistermaat
  137. Thomas Illig
  138. Aaron Isaacs
  139. Alan L. James
  140. Janina Jeff
  141. Berit Johansen
  142. Åsa Johansson
  143. Jennifer Jolley
  144. Thorhildur Juliusdottir
  145. Juhani Junttila
  146. Abel N. Kho
  147. Leena Kinnunen
  148. Norman Klopp
  149. Thomas Kocher
  150. Wolfgang Kratzer
  151. Peter Lichtner
  152. Lars Lind
  153. Jaana Lindstrom
  154. Stéphane Lobbens
  155. Mattias Lorentzon
  156. Yingchang Lu
  157. Valeriya Lyssenko
  158. Patrik K. E. Magnusson
  159. Anubha Mahajan
  160. Marc Maillard
  161. Wendy L. McArdle
  162. Colin A. McKenzie
  163. Stela McLachlan
  164. Paul J. McLaren
  165. Cristina Menni
  166. Sigrun Merger
  167. Lili Milani
  168. Alireza Moayyeri
  169. Keri L. Monda
  170. Mario A. Morken
  171. Gabriele Müller
  172. Martina Muller-Nurasyid
  173. Arthur W. Musk
  174. Narisu Narisu
  175. Matthias Nauck
  176. Ilja M. Nolte
  177. Markus M. Nothen
  178. Laticia Oozageer
  179. Stefan Pilz
  180. Nigel W. Rayner
  181. Frida Renström
  182. Neil R. Robertson
  183. Lynda M. Rose
  184. Ronan Roussel
  185. Serena Sanna
  186. Hubert Scharnagl
  187. Salome Scholtens
  188. Fredrick R. Schumacher
  189. Heribert Schunkert
  190. Robert A. Scott
  191. Joban Sehmi
  192. Thomas Seufferlein
  193. Jianxin Shi
  194. Karri Silventoinen
  195. Johannes H. Smit
  196. Albert Vernon Smith
  197. Joanna Smolonska
  198. Alice V. Stanton
  199. Kathleen Stirrups
  200. David J. Stott
  201. Heather M. Stringham
  202. Johan Sundström
  203. Morris A. Swertz
  204. Ann-Christine Syvänen
  205. Bamidele O. Tayo
  206. Gudmar Thorleifsson
  207. Jonathan P. Tyrer
  208. Suzanne van Dijk
  209. Natasja M. van Schoor
  210. Nathalie van der Velde
  211. Diana van Heemst
  212. Floor V. A. van Oort
  213. Sita H. Vermeulen
  214. Niek Verweij
  215. Judith M. Vonk
  216. Lindsay L. Waite
  217. Melanie Waldenberger
  218. Roman Wennauer
  219. Lynne R. Wilkens
  220. Christina Willenborg
  221. Tom Wilsgaard
  222. Mary K. Wojczynski
  223. Andrew Wong
  224. Alan F. Wright
  225. Qunyuan Zhang
  226. Dominique Arveiler
  227. Stephan J. L. Bakker
  228. John Beilby
  229. Richard N. Bergman
  230. Sven Bergmann
  231. Reiner Biffar
  232. John Blangero
  233. Dorret I. Boomsma
  234. Stefan R. Bornstein
  235. Pascal Bovet
  236. Paolo Brambilla
  237. Morris J. Brown
  238. Harry Campbell
  239. Mark J. Caulfield
  240. Aravinda Chakravarti
  241. Rory Collins
  242. Francis S. Collins
  243. Dana C. Crawford
  244. L. Adrienne Cupples
  245. John Danesh
  246. Ulf de Faire
  247. Hester M. den Ruijter
  248. Raimund Erbel
  249. Jeanette Erdmann
  250. Johan G. Eriksson
  251. Martin Farrall
  252. Ele Ferrannini
  253. Ian Ford
  254. Nita G. Forouhi
  255. Terrence Forrester
  256. Ron T. Gansevoort
  257. Pablo V. Gejman
  258. Christian Gieger
  259. Alain Golay
  260. Omri Gottesman
  261. Vilmundur Gudnason
  262. Ulf Gyllensten
  263. David W. Haas
  264. Alistair S. Hall
  265. Tamara B. Harris
  266. Andrew T. Hattersley
  267. Andrew C. Heath
  268. Christian Hengstenberg
  269. Andrew A. Hicks
  270. Lucia A. Hindorff
  271. Aroon D. Hingorani
  272. Albert Hofman
  273. G. Kees Hovingh
  274. Steve E. Humphries
  275. Steven C. Hunt
  276. Elina Hypponen
  277. Kevin B. Jacobs
  278. Marjo-Riitta Jarvelin
  279. Pekka Jousilahti
  280. Antti M. Jula
  281. Jaakko Kaprio
  282. John J. P. Kastelein
  283. Manfred Kayser
  284. Frank Kee
  285. Sirkka M. Keinanen-Kiukaanniemi
  286. Lambertus A. Kiemeney
  287. Jaspal S. Kooner
  288. Charles Kooperberg
  289. Seppo Koskinen
  290. Peter Kovacs
  291. Aldi T. Kraja
  292. Meena Kumari
  293. Johanna Kuusisto
  294. Timo A. Lakka
  295. Claudia Langenberg
  296. Loic Le Marchand
  297. Terho Lehtimaki
  298. Sara Lupoli
  299. Pamela A. F. Madden
  300. Satu Mannisto
  301. Paolo Manunta
  302. Andre Marette
  303. Tara C. Matise
  304. Barbara McKnight
  305. Thomas Meitinger
  306. Frans L. Moll
  307. Grant W. Montgomery
  308. Andrew D. Morris
  309. Andrew P. Morris
  310. Jeffrey C. Murray
  311. Mari Nelis
  312. Claes Ohlsson
  313. Albertine J. Oldehinkel
  314. Ken K. Ong
  315. Willem H. Ouwehand
  316. Gerard Pasterkamp
  317. Annette Peters
  318. Peter P. Pramstaller
  319. Jackie F. Price
  320. Lu Qi
  321. Olli T. Raitakari
  322. Tuomo Rankinen
  323. D. C. Rao
  324. Treva K. Rice
  325. Marylyn Ritchie
  326. Igor Rudan
  327. Veikko Salomaa
  328. Nilesh J. Samani
  329. Jouko Saramies
  330. Mark A. Sarzynski
  331. Peter E. H. Schwarz
  332. Sylvain Sebert
  333. Peter Sever
  334. Alan R. Shuldiner
  335. Juha Sinisalo
  336. Valgerdur Steinthorsdottir
  337. Ronald P. Stolk
  338. Jean-Claude Tardif
  339. Anke Tonjes
  340. Angelo Tremblay
  341. Elena Tremoli
  342. Jarmo Virtamo
  343. Marie-Claude Vohl
  344. Philippe Amouyel
  345. Folkert W. Asselbergs
  346. Themistocles L. Assimes
  347. Murielle Bochud
  348. Bernhard O. Boehm
  349. Eric Boerwinkle
  350. Erwin P. Bottinger
  351. Claude Bouchard
  352. Stephane Cauchi
  353. John C. Chambers
  354. Stephen J. Chanock
  355. Richard S. Cooper
  356. Paul I. W. de Bakker
  357. George Dedoussis
  358. Luigi Ferrucci
  359. Paul W. Franks
  360. Philippe Froguel
  361. Leif C. Groop
  362. Christopher A. Haiman
  363. Anders Hamsten
  364. M. Geoffrey Hayes
  365. Jennie Hui
  366. David J. Hunter
  367. Kristian Hveem
  368. J. Wouter Jukema
  369. Robert C. Kaplan
  370. Mika Kivimaki
  371. Diana Kuh
  372. Markku Laakso
  373. Yongmei Liu
  374. Nicholas G. Martin
  375. Winfried März
  376. Mads Melbye
  377. Susanne Moebus
  378. Patricia B. Munroe
  379. Inger Njølstad
  380. Ben A. Oostra
  381. Colin N. A. Palmer
  382. Nancy L. Pedersen
  383. Markus Perola
  384. Louis Perusse
  385. Ulrike Peters
  386. Joseph E. Powell
  387. Chris Power
  388. Thomas Quertermous
  389. Rainer Rauramaa
  390. Eva Reinmaa
  391. Paul M. Ridker
  392. Fernando Rivadeneira
  393. Jerome I. Rotter
  394. Timo E. Saaristo
  395. Danish Saleheen
  396. David Schlessinger
  397. P. Eline Slagboom
  398. Harold Snieder
  399. Tim D. Spector
  400. Konstantin Strauch
  401. Michael Stumvoll
  402. Jaakko Tuomilehto
  403. Matti Uusitupa
  404. Pim van der Harst
  405. Henry Volzke
  406. Mark Walker
  407. Nicholas J. Wareham
  408. Hugh Watkins
  409. H. Erich Wichmann
  410. James F. Wilson
  411. Pieter Zanen
  412. Panos Deloukas
  413. Iris M. Heid
  414. Cecilia M. Lindgren
  415. Karen L. Mohlke
  416. Elizabeth K. Speliotes
  417. Unnur Thorsteinsdottir
  418. Ines Barroso
  419. Caroline S. Fox
  420. Kari E. North
  421. David P. Strachan
  422. Jacques S. Beckmann
  423. Sonja I. Berndt
  424. Michael Boehnke
  425. Ingrid B. Borecki
  426. Mark I. McCarthy
  427. Andres Metspalu
  428. Kari Stefansson
  429. Andre G. Uitterlinden
  430. Cornelia M. van Duijn
  431. Lude Franke
  432. Cristen J. Willer
  433. Alkes L. Price
  434. Guillaume Lettre
  435. Ruth J. F. Loos
  436. Michael N. Weedon
  437. Erik Ingelsson
  438. Jeffrey R. O'Connell
  439. Goncalo R. Abecasis
  440. Daniel I. Chasman
  441. Michael E. Goddard
  442. Peter M. Visscher
  443. Joel N. Hirschhorn
  444. Timothy M. Frayling

Publication date

2014

Summary

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.

Published in

Nature Genetics

Volume and page numbers

46 , 1173 -1186

DOI

http://dx.doi.org/10.1038/ng.3097

ISSN

16

Subjects

Medicine, Science And Technology, and Biology

Links

University of Essex, Albert Sloman Library Periodicals *restricted to University of Essex registered users* - http://serlib0.essex.ac.uk/record=b1680801~S5

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