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Journal Article

The influence of age and sex on genetic associations with adult body size and shape: a large-scale genome-wide interaction study

Authors

  1. Thomas W. Winkler
  2. Anne E. Justice
  3. Mariaelisa Graff
  4. Llilda Barata
  5. Mary F. Feitosa
  6. Su Chu
  7. Jacek Czajkowski
  8. Tonu Esko
  9. Tove Fall
  10. Tuomas O. Kilpeläinen
  11. Reedik Mägi
  12. Evelin Mihailov
  13. Tune H. Pers
  14. Sina Rüeger
  15. Alexander Teumer
  16. Georg B. Ehret
  17. Teresa Ferreira
  18. Nancy L. Heard-Costa
  19. Juha Karjalainen
  20. Vasiliki Lagou
  21. Anubha Mahajan
  22. Michael D. Neinast
  23. Inga Prokopenko
  24. Jeannette Simino
  25. Tanya M. Teslovich
  26. Rick Jansen
  27. Harm-Jan Westra
  28. Charles C. White
  29. Devin Absher
  30. Tarunveer Singh Ahluwalia
  31. Shafqat Ahmad
  32. Eva Albrecht
  33. Alexessander Couto Alves
  34. Jennifer L. Bragg-Gresham
  35. Anton J. M. de Craen
  36. Joshua C. Bis
  37. Amélie Bonnefond
  38. Gabrielle Boucher
  39. Gemma Cadby
  40. Yu-Ching Cheng
  41. Charleston W. K. Chiang
  42. Graciela Delgado
  43. Ayse Demirkan
  44. Nicole Dueker
  45. Niina Eklund
  46. Gudny Eiriksdottir
  47. Joel Eriksson
  48. Bjarke Feenstra
  49. Krista Fischer
  50. Francesca Frau
  51. Tessel E. Galesloot
  52. Frank Geller
  53. Anuj Goel
  54. Mathias Gorski
  55. Tanja B. Grammer
  56. Stefan Gustafsson
  57. Saskia Haitjema
  58. Jouke-Jan Hottenga
  59. Jennifer E. Huffman
  60. Anne U. Jackson
  61. Kevin B. Jacobs
  62. Åsa Johansson
  63. Marika Kaakinen
  64. Marcus E. Kleber
  65. Jari Lahti
  66. Irene Mateo Leach
  67. Benjamin Lehne
  68. Youfang Liu
  69. Ken Sin Lo
  70. Mattias Lorentzon
  71. Jian'an Luan
  72. Pamela A.F. Madden
  73. Massimo Mangino
  74. Barbara McKnight
  75. Carolina Medina-Gomez
  76. Keri L. Monda
  77. May E. Montasser
  78. Gabriele Müller
  79. Martina Müller-Nurasyid
  80. Ilja M. Nolte
  81. Kalliope Panoutsopoulou
  82. Laura Pascoe
  83. Lavinia Paternoster
  84. Nigel W. Rayner
  85. Frida Renström
  86. Federica Rizzi
  87. Lynda M. Rose
  88. Kathy A. Ryan
  89. Perttu Salo
  90. Serena Sanna
  91. Hubert Scharnagl
  92. Jianxin Shi
  93. Albert Vernon Smith
  94. Lorraine Southam
  95. Alena Stančáková
  96. Valgerdur Steinthorsdottir
  97. Rona J. Strawbridge
  98. Yun Ju Sung
  99. Ioanna Tachmazidou
  100. Toshiko Tanaka
  101. Gudmar Thorleifsson
  102. Stella Trompet
  103. Natalia Pervjakova
  104. Jonathan P. Tyrer
  105. Liesbeth Vandenput
  106. Sander W. van der Laan
  107. Nathalie van der Velde
  108. Jessica van Setten
  109. Jana V. van Vliet-Ostaptchouk
  110. Niek Verweij
  111. Efthymia Vlachopoulou
  112. Lindsay L. Waite
  113. Sophie R. Wang
  114. Zhaoming Wang
  115. Sarah H. Wild
  116. Christina Willenborg
  117. James F. Wilson
  118. Andrew Wong
  119. Jian Yang
  120. Loïc Yengo
  121. Laura M. Yerges-Armstrong
  122. Lei Yu
  123. Weihua Zhang
  124. Jing Hua Zhao
  125. Ehm A. Andersson
  126. Stephan J. L. Bakker
  127. Damiano Baldassarre
  128. Karina Banasik
  129. Matteo Barcella
  130. Cristina Barlassina
  131. Claire Bellis
  132. Paola Benaglio
  133. John Blangero
  134. Matthias Blüher
  135. Fabrice Bonnet
  136. Lori L. Bonnycastle
  137. Heather A. Boyd
  138. Marcel Bruinenberg
  139. Aron S. Buchman
  140. Harry Campbell
  141. Yii-Der Ida Chen
  142. Peter S. Chines
  143. Simone Claudi-Boehm
  144. John Cole
  145. Francis S. Collins
  146. Eco J.C. de Geus
  147. Lisette C.P.G.M. de Groot
  148. Maria Dimitriou
  149. Jubao Duan
  150. Stefan Enroth
  151. Elodie Eury
  152. Aliki-Eleni Farmaki
  153. Nita G. Forouhi
  154. Nele Friedrich
  155. Pablo V. Gejman
  156. Bruna Gigante
  157. Nicola Glorioso
  158. Alan S. Go
  159. Omri Gottesman
  160. Jürgen Gräßler
  161. Harald Grallert
  162. Niels Grarup
  163. Yu-Mei Gu
  164. Linda Broer
  165. Annelies C. Ham
  166. Torben Hansen
  167. Tamara B. Harris
  168. Catharina A. Hartman
  169. Maija Hassinen
  170. Nicholas Hastie
  171. Andrew T. Hattersley
  172. Andrew C. Heath
  173. Anjali K. Henders
  174. Dena Hernandez
  175. Hans Hillege
  176. Oddgeir Holmen
  177. Kees G. Hovingh
  178. Jennie Hui
  179. Lise L. Husemoen
  180. Nina Hutri-Kähönen
  181. Pirro G. Hysi
  182. Thomas Illig
  183. Philip L. De Jager
  184. Shapour Jalilzadeh
  185. Torben Jørgensen
  186. Markus Juonala
  187. Stavroula Kanoni
  188. Maria Karaleftheri
  189. Kay Tee Khaw
  190. Leena Kinnunen
  191. Steven J. Kittner
  192. Wolfgang Koenig
  193. Ivana Kolcic
  194. Peter Kovacs
  195. Nikolaj T. Krarup
  196. Wolfgang Kratzer
  197. Janine Krüger
  198. Diana Kuh
  199. Meena Kumari
  200. Theodosios Kyriakou
  201. Claudia Langenberg
  202. Lars Lannfelt
  203. Chiara Lanzani
  204. Vaneet Lotay
  205. Lenore J. Launer
  206. Karin Leander
  207. Jaana Lindström
  208. Allan Linneberg
  209. Yan-Ping Liu
  210. Stéphane Lobbens
  211. Robert Luben
  212. Valeriya Lyssenko
  213. Satu Männistö
  214. Patrik K. Magnusson
  215. Wendy L. McArdle
  216. Cristina Menni
  217. Sigrun Merger
  218. Lili Milani
  219. Grant W. Montgomery
  220. Andrew P. Morris
  221. Narisu Narisu
  222. Mari Nelis
  223. Ken K. Ong
  224. Aarno Palotie
  225. Louis Pérusse
  226. Irene Pichler
  227. Maria G. Pilia
  228. Anneli Pouta
  229. Myriam Rheinberger
  230. Rasmus Ribel-Madsen
  231. Marcus Richards
  232. Kenneth M. Rice
  233. Treva K. Rice
  234. Carlo Rivolta
  235. Veikko Salomaa
  236. Alan R. Sanders
  237. Mark A. Sarzynski
  238. Salome Scholtens
  239. Robert A. Scott
  240. William R. Scott
  241. Sylvain Sebert
  242. Sebanti Sengupta
  243. Bengt Sennblad
  244. Thomas Seufferlein
  245. Angela Silveira
  246. P. Eline Slagboom
  247. Jan H. Smit
  248. Thomas H. Sparsø
  249. Kathleen Stirrups
  250. Ronald P. Stolk
  251. Heather M. Stringham
  252. Morris A. Swertz
  253. Amy J. Swift
  254. Ann-Christine Syvänen
  255. Sian-Tsung Tan
  256. Barbara Thorand
  257. Anke Tönjes
  258. Angelo Tremblay
  259. Emmanouil Tsafantakis
  260. Peter J. van der Most
  261. Uwe Völker
  262. Marie-Claude Vohl
  263. Judith M. Vonk
  264. Melanie Waldenberger
  265. Ryan W. Walker
  266. Roman Wennauer
  267. Elisabeth Widén
  268. Gonneke Willemsen
  269. Tom Wilsgaard
  270. Alan F. Wright
  271. M. Carola Zillikens
  272. Suzanne C. van Dijk
  273. Natasja M. van Schoor
  274. Folkert W. Asselbergs
  275. Paul I. W. de Bakker
  276. Jacques S. Beckmann
  277. John Beilby
  278. David A. Bennett
  279. Richard N. Bergman
  280. Sven Bergmann
  281. Carsten A. Böger
  282. Bernhard O. Boehm
  283. Eric Boerwinkle
  284. Dorret I. Boomsma
  285. Stefan R. Bornstein
  286. Erwin P. Bottinger
  287. Claude Bouchard
  288. John C. Chambers
  289. Stephen J. Chanock
  290. Daniel I. Chasman
  291. Francesco Cucca
  292. George Dedoussis
  293. Jeanette Erdmann
  294. Johan G. Eriksson
  295. Denis A. Evans
  296. Ulf de Faire
  297. Martin Farrall
  298. Luigi Ferrucci
  299. Ian Ford
  300. Lude Franke
  301. Paul W. Franks
  302. Philippe Froguel
  303. Ron T. Gansevoort
  304. Christian Gieger
  305. Henrik Grönberg
  306. Vilmundur Gudnason
  307. Ulf Gyllensten
  308. Per Hall
  309. Anders Hamsten
  310. Pim van der Harst
  311. Caroline Hayward
  312. Markku Heliövaara
  313. Christian Hengstenberg
  314. Andrew A. Hicks
  315. Aroon Hingorani
  316. Albert Hofman
  317. Frank Hu
  318. Heikki V. Huikuri
  319. Kristian Hveem
  320. Alan L. James
  321. Joanne M. Jordan
  322. Antti Jula
  323. Mika Kähönen
  324. Eero Kajantie
  325. Sekar Kathiresan
  326. Lambertus A.L.M. Kiemeney
  327. Mika Kivimaki
  328. Paul B. Knekt
  329. Heikki A. Koistinen
  330. Jaspal S. Kooner
  331. Seppo Koskinen
  332. Johanna Kuusisto
  333. Winfried Maerz
  334. Nicholas G. Martin
  335. Markku Laakso
  336. Timo A. Lakka
  337. Terho Lehtimäki
  338. Guillaume Lettre
  339. Douglas F. Levinson
  340. Lars Lind
  341. Marja-Liisa Lokki
  342. Pekka Mäntyselkä
  343. Mads Melbye
  344. Andres Metspalu
  345. Braxton D. Mitchell
  346. Frans L. Moll
  347. Jeffrey C. Murray
  348. Arthur W. Musk
  349. Markku S. Nieminen
  350. Inger Njølstad
  351. Claes Ohlsson
  352. Albertine J. Oldehinkel
  353. Ben A. Oostra
  354. Lyle J. Palmer
  355. James S. Pankow
  356. Gerard Pasterkamp
  357. Nancy L. Pedersen
  358. Oluf Pedersen
  359. Brenda W. Penninx
  360. Markus Perola
  361. Annette Peters
  362. Ozren Polasek
  363. Peter P. Pramstaller
  364. Bruce M. Psaty
  365. Lu Qi
  366. Thomas Quertermous
  367. Olli T. Raitakari
  368. Tuomo Rankinen
  369. Rainer Rauramaa
  370. Paul M. Ridker
  371. John D. Rioux
  372. Fernando Rivadeneira
  373. Jerome I. Rotter
  374. Igor Rudan
  375. Hester M. den Ruijter
  376. Juha Saltevo
  377. Naveed Sattar
  378. Heribert Schunkert
  379. Peter E.H. Schwarz
  380. Alan R. Shuldiner
  381. Juha Sinisalo
  382. Harold Snieder
  383. Thorkild I. A. Sørensen
  384. Tim D. Spector
  385. Jan A. Staessen
  386. Stefania Bandinelli
  387. Unnur Thorsteinsdottir
  388. Michael Stumvoll
  389. Jean-Claude Tardif
  390. Elena Tremoli
  391. Jaakko Tuomilehto
  392. André G. Uitterlinden
  393. Matti Uusitupa
  394. André L.M. Verbeek
  395. Sita H. Vermeulen
  396. Jorma S. Viikari
  397. Veronique Vitart
  398. Henry Völzke
  399. Peter Vollenweider
  400. Gérard Waeber
  401. Mark Walker
  402. Henri Wallaschofski
  403. Nicholas J. Wareham
  404. Hugh Watkins
  405. Eleftheria Zeggini
  406. Aravinda Chakravarti
  407. Deborah J. Clegg
  408. L. Adrienne Cupples
  409. Penny Gordon-Larsen
  410. Cashell E. Jaquish
  411. D.C. Rao
  412. Goncalo R. Abecasis
  413. Themistocles L. Assimes
  414. Inês Barroso
  415. Sonja I. Berndt
  416. Michael Boehnke
  417. Panos Deloukas
  418. Caroline S. Fox
  419. Leif C. Groop
  420. David J. Hunter
  421. Erik Ingelsson
  422. Robert C. Kaplan
  423. Mark I. McCarthy
  424. Karen L. Mohlke
  425. Jeffrey R. O'Connell
  426. David Schlessinger
  427. David P. Strachan
  428. Kari Stefansson
  429. Cornelia M. van Duijn
  430. Joel N. Hirschhorn
  431. Cecilia M. Lindgren
  432. Iris M. Heid
  433. Kari E. North
  434. Ingrid B. Borecki
  435. Zoltán Kutalik
  436. Ruth J. F. Loos

Publication date

Oct 2015

Summary

Adult body size and body shape differ substantially between men and women and change over time. More than 100 genetic variants that influence body mass index (measure of body size) or waist-to-hip ratio (measure of body shape) have been identified. While there is evidence that some genetic loci affect body shape differently in men than in women, little is known about whether genetic effects differ in older compared to younger adults, and whether such changes differ between men and women. Therefore, we conducted a systematic genome-wide search, including 114 studies (>320,000 individuals), to specifically identify genetic loci with age- and or sex-dependent effects on body size and shape. We identified 15 loci of which the effect on BMI was different in older compared to younger adults, whereas we found no evidence for loci with different effects in men compared to women. The opposite was seen for body shape as we identified 44 loci of which the effect on waist-to-hip ratio differed between men and women, but no difference between younger and older adults were observed. Our observations may provide new insights into the biology that underlies weight change with age or the sexual dimorphism of body shape.

Published in

PLoS Genetics

Volume

11

DOI

http://dx.doi.org/10.1371/journal.pgen.1005378

ISSN

16

Subjects

Medicine, Science And Technology, Research, Health, and Biology

Notes

Open access article; This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication

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