Associations of autozygosity with a broad range of human phenotypes

Publication type

Journal Article

Authors

  1. David W. Clark
  2. Yukinori Okada
  3. Kristjan H.S. Moore
  4. Dan Mason
  5. Nicola Pirastu
  6. Ilaria Gandin
  7. Hannele Mattsson
  8. Catriona L.K. Barnes
  9. Kuang Lin
  10. Jing Hua Zhao
  11. Patrick Deelen
  12. Rebecca Rohde
  13. Claudia Schurmann
  14. Xiuqing Guo
  15. Franco Giulianini
  16. Weihua Zhang
  17. Carolina Medina-Gomez
  18. Robert Karlsson
  19. Yanchun Bao
  20. Traci M. Bartz
  21. Clemens Baumbach
  22. Ginevra Biino
  23. Matthew J. Bixley
  24. Marco Brumat
  25. Jin-Fang Chai
  26. Tanguy Corre
  27. Diana L. Cousminer
  28. Annelot M. Dekker
  29. David A. Eccles
  30. Kristel R. van Eijk
  31. Christian Fuchsberger
  32. He Gao
  33. Marine Germain
  34. Scott D. Gordon
  35. Hugoline G. de Haan
  36. Sarah E. Harris
  37. Edith Hofer
  38. Alicia Huerta-Chagoya
  39. Catherine Igartua
  40. Iris E. Jansen
  41. Yucheng Jia
  42. Tim Kacprowski
  43. Torgny Karlsson
  44. Marcus E. Kleber
  45. Shengchao Alfred Li
  46. Ruifang Li-Gao
  47. Anubha Mahajan
  48. Koichi Matsuda
  49. Karina Meidtner
  50. Weihua Meng
  51. May E. Montasser
  52. Peter J. van der Most
  53. Matthias Munz
  54. Teresa Nutile
  55. Teemu Palviainen
  56. Gauri Prasad
  57. Rashmi B. Prasad
  58. Tallapragada Divya Sri Priyanka
  59. Federica Rizzi
  60. Erika Salvi
  61. Bishwa R. Sapkota
  62. Daniel Shriner
  63. Line Skotte
  64. Melissa Smart
  65. Albert Vernon Smith
  66. Ashley van der Spek
  67. Cassandra N. Spracklen
  68. Rona J. Strawbridge
  69. Salman M. Tajuddin
  70. Stella Trompet
  71. Constance Turman
  72. Niek Verweij
  73. Clara Viberti
  74. Lihua Wang
  75. Helen R. Warren
  76. Robyn E. Wootton
  77. Lisa R. Yanek
  78. Jie Yao
  79. Noha A. Yousri
  80. Wei Zhao
  81. Adebowale A. Adeyemo
  82. Saima Afaq
  83. Carlos Alberto Aguilar-Salinas
  84. Masato Akiyama
  85. Matthew L. Albert
  86. Matthew A. Allison
  87. Maris Alver
  88. Tin Aung
  89. Fereidoun Azizi
  90. Amy R. Bentley
  91. Heiner Boeing
  92. Eric Boerwinkle
  93. Judith B. Borja
  94. Gert J. de Borst
  95. Erwin P. Bottinger
  96. Linda Broer
  97. Harry Campbell
  98. Stephen Chanock
  99. Miao-Li Chee
  100. Guanjie Chen
  101. Yii-Der I. Chen
  102. Zhengming Chen
  103. Yen-Feng Chiu
  104. Massimiliano Cocca
  105. Francis S. Collins
  106. Maria Pina Concas
  107. Janie Corley
  108. Giovanni Cugliari
  109. Rob M. van Dam
  110. Anna Damulina
  111. Maryam S. Daneshpour
  112. Felix R. Day
  113. Graciela E. Delgado
  114. Klodian Dhana
  115. Alexander S.F. Doney
  116. Marcus Dörr
  117. Ayo P. Doumatey
  118. Nduna Dzimiri
  119. S. Sunna Ebenesersdóttir
  120. Joshua Elliott
  121. Paul Elliott
  122. Ralf Ewert
  123. Janine F. Felix
  124. Krista Fischer
  125. Barry I. Freedman
  126. Giorgia Girotto
  127. Anuj Goel
  128. Martin Gögele
  129. Mark O. Goodarzi
  130. Mariaelisa Graff
  131. Einat Granot-Hershkovitz
  132. Francine Grodstein
  133. Simonetta Guarrera
  134. Daniel F. Gudbjartsson
  135. Kamran Guity
  136. Bjarni Gunnarsson
  137. Yu Guo
  138. Saskia P. Hagenaars
  139. Christopher A. Haiman
  140. Avner Halevy
  141. Tamara B. Harris
  142. Mehdi Hedayati
  143. David A. van Heel
  144. Makoto Hirata
  145. Imo Höfer
  146. Chao Agnes Hsiung
  147. Jinyan Huang
  148. Yi-Jen Hung
  149. M. Arfan Ikram
  150. Anuradha Jagadeesan
  151. Pekka Jousilahti
  152. Yoichiro Kamatani
  153. Masahiro Kanai
  154. Nicola D. Kerrison
  155. Thorsten Kessler
  156. Kay-Tee Khaw
  157. Chiea Chuen Khor
  158. Dominique P.V. de Kleijn
  159. Woon-Puay Koh
  160. Ivana Kolcic
  161. Peter Kraft
  162. Bernhard K. Krämer
  163. Zoltán Kutalik
  164. Johanna Kuusisto
  165. Claudia Langenberg
  166. Lenore J. Launer
  167. Deborah A. Lawlor
  168. I-Te Lee
  169. Wen-Jane Lee
  170. Markus M. Lerch
  171. Liming Li
  172. Jianjun Liu
  173. Marie Loh
  174. Stephanie J. London
  175. Stephanie Loomis
  176. Yingchang Lu
  177. Jian’an Luan
  178. Reedik Mägi
  179. Ani W. Manichaikul
  180. Paolo Manunta
  181. Gisli Masson
  182. Nana Matoba
  183. Xue W. Mei
  184. Christa Meisinger
  185. Thomas Meitinger
  186. Massimo Mezzavilla
  187. Lili Milani
  188. Iona Y. Millwood
  189. Yukihide Momozawa
  190. Amy Moore
  191. Pierre-Emmanuel Morange
  192. Hortensia Moreno-Macías
  193. Trevor A. Mori
  194. Alanna C. Morrison
  195. Taulant Muka
  196. Yoshinori Murakami
  197. Alison D. Murray
  198. Renée de Mutsert
  199. Josyf C. Mychaleckyj
  200. Mike A. Nalls
  201. Matthias Nauck
  202. Matt J. Neville
  203. Ilja M. Nolte
  204. Ken K. Ong
  205. Lorena Orozco
  206. Sandosh Padmanabhan
  207. Gunnar Pálsson
  208. James S. Pankow
  209. Cristian Pattaro
  210. Alison Pattie
  211. Ozren Polasek
  212. Neil Poulter
  213. Peter P. Pramstaller
  214. Lluis Quintana-Murci
  215. Katri Räikkönen
  216. Sarju Ralhan
  217. Dabeeru C. Rao
  218. Wouter van Rheenen
  219. Stephen S. Rich
  220. Paul M. Ridker
  221. Cornelius A. Rietveld
  222. Antonietta Robino
  223. Frank J.A. van Rooij
  224. Daniela Ruggiero
  225. Yasaman Saba
  226. Sabanayagam Charumathi
  227. Maria Sabater-Lleal
  228. Cinzia Felicita Sala
  229. Veikko Salomaa
  230. Kevin Sandow
  231. Helena Schmidt
  232. Laura J. Scott
  233. William R. Scott
  234. Bahareh Sedaghati-Khayat
  235. Bengt Sennblad
  236. Jessica van Setten
  237. Peter J. Sever
  238. Wayne H.-H. Sheu
  239. Yuan Shi
  240. Smeeta Shrestha
  241. Sharvari Rahul Shukla
  242. Jon K. Sigurdsson
  243. Timo Tonis Sikka
  244. Jai Rup Singh
  245. Blair H. Smith
  246. Alena Stančáková
  247. Alice Stanton
  248. John M. Starr
  249. Lilja Stefansdottir
  250. Leon Straker
  251. Patrick Sulem
  252. Gardar Sveinbjornsson
  253. Morris A. Swertz
  254. Adele M. Taylor
  255. Kent D. Taylor
  256. Natalie Terzikhan
  257. Yih-Chung Tham
  258. Gudmar Thorleifsson
  259. Unnur Thorsteinsdottir
  260. Annika Tillander
  261. Russell P. Tracy
  262. Teresa Tusié-Luna
  263. Ioanna Tzoulaki
  264. Simona Vaccargiu
  265. Jagadish Vangipurapu
  266. Jan H. Veldink
  267. Veronique Vitart
  268. Uwe Völker
  269. Eero Vuoksimaa
  270. Salma M. Wakil
  271. Melanie Waldenberger
  272. Gurpreet S. Wander
  273. Ya Xing Wang
  274. Nicholas J. Wareham
  275. Sarah Wild
  276. Chittaranjan S. Yajnik
  277. Jian-Min Yuan
  278. Lingyao Zeng
  279. Liang Zhang
  280. Jie Zhou
  281. Najaf Amin
  282. Folkert W. Asselbergs
  283. Stephan J. L. Bakker
  284. Diane M. Becker
  285. Benjamin Lehne
  286. David A. Bennett
  287. Leonard H. van den Berg
  288. Sonja I. Berndt
  289. Dwaipayan Bharadwaj
  290. Lawrence F. Bielak
  291. Murielle Bochud
  292. Mike Boehnke
  293. Claude Bouchard
  294. Jonathan P. Bradfield
  295. Jennifer A. Brody
  296. Archie Campbell
  297. Shai Carmi
  298. Mark J. Caulfield
  299. David Cesarini
  300. John C. Chambers
  301. Giriraj Ratan Chandak
  302. Ching-Yu Cheng
  303. Marina Ciullo
  304. Marilyn Cornelis
  305. Daniele Cusi
  306. George Davey Smith
  307. Ian J. Deary
  308. Rajkumar Dorajoo
  309. Cornelia M. van Duijn
  310. David Ellinghaus
  311. Jeanette Erdmann
  312. Johan G. Eriksson
  313. Evangelos Evangelou
  314. Michele K. Evans
  315. Jessica D. Faul
  316. Bjarke Feenstra
  317. Mary Feitosa
  318. Sylvain Foisy
  319. Andre Franke
  320. Yechiel Friedlander
  321. Paolo Gasparini
  322. Christian Gieger
  323. Clicerio Gonzalez
  324. Philippe Goyette
  325. Struan F. A. Grant
  326. Lyn R. Griffiths
  327. Leif Groop
  328. Vilmundur Gudnason
  329. Ulf Gyllensten
  330. Hakon Hakonarson
  331. Anders Hamsten
  332. Pim van der Harst
  333. Chew-Kiat Heng
  334. Andrew A. Hicks
  335. Hagit Hochner
  336. Heikki Huikuri
  337. Steven C. Hunt
  338. Vincent W. V. Jaddoe
  339. Philip L. De Jager
  340. Magnus Johannesson
  341. Åsa Johansson
  342. Jost B. Jonas
  343. J. Wouter Jukema
  344. Juhani Junttila
  345. Jaakko Kaprio
  346. Sharon L. R. Kardia
  347. Fredrik Karpe
  348. Meena Kumari
  349. Markku Laakso
  350. Sander W. van der Laan
  351. Jari Lahti
  352. Matthias Laudes
  353. Rodney A. Lea
  354. Wolfgang Lieb
  355. Thomas Lumley
  356. Nicholas G. Martin
  357. Winfried März
  358. Giuseppe Matullo
  359. Mark I. McCarthy
  360. Sarah E. Medland
  361. Tony R. Merriman
  362. Andres Metspalu
  363. Brian F. Meyer
  364. Karen L. Mohlke
  365. Grant W. Montgomery
  366. Dennis Mook-Kanamori
  367. Patricia B. Munroe
  368. Kari E. North
  369. Dale R. Nyholt
  370. Jeffrey R. O’Connell
  371. Carole Ober
  372. Albertine J. Oldehinkel
  373. Walter Palmas
  374. Colin Palmer
  375. Gerard G. Pasterkamp
  376. Etienne Patin
  377. Craig E. Pennell
  378. Louis Perusse
  379. Patricia A. Peyser
  380. Mario Pirastu
  381. Tinca J.C. Polderman
  382. David J. Porteous
  383. Danielle Posthuma
  384. Bruce M. Psaty
  385. John D. Rioux
  386. Fernando Rivadeneira
  387. Charles Rotimi
  388. Jerome I. Rotter
  389. Igor Rudan
  390. Hester M. den Ruijter
  391. E. Shyong Tai
  392. Alexander Teumer
  393. Nicholas J. Timpson
  394. Daniela Toniolo
  395. David-Alexandre Tregouet
  396. Tiinamaija Tuomi
  397. Peter Vollenweider
  398. Carol A. Wang
  399. David R. Weir
  400. John B. Whitfield
  401. Cisca Wijmenga
  402. Tien-Yin Wong
  403. John Wright
  404. Jingyun Yang
  405. Lei Yu
  406. Babette S. Zemel
  407. Alan B. Zonderman
  408. Markus Perola
  409. Patrik K.E. Magnusson
  410. André G. Uitterlinden
  411. Jaspal S. Kooner
  412. Daniel I. Chasman
  413. Ruth J.F. Loos
  414. Nora Franceschini
  415. Lude Franke
  416. Chris S. Haley
  417. Caroline Hayward
  418. Robin G. Walters
  419. John R.B. Perry
  420. Tõnu Esko
  421. Agnar Helgason
  422. Kari Stefansson
  423. Peter K. Joshi
  424. Michiaki Kubo
  425. James F. Wilson

Publication date

October 15, 2019

Summary:

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.

Published in

Nature Communications

Volume

Volume: 10:4957

DOI

https://doi.org/10.1038/s41467-019-12283-6

ISSN

20411723

Subjects

Notes

Open Access

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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