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A Saturated Map of Common Genetic Variants Associated With Human Height Publisher Pubmed



Yengo L1 ; Vedantam S2, 3 ; Marouli E4 ; Sidorenko J1 ; Bartell E2, 3, 5 ; Sakaue S3, 6, 7, 8 ; Graff M9 ; Eliasen AU10, 11 ; Jiang Y12 ; Raghavan S13, 14 ; Miao J2, 3 ; Arias JD15 ; Graham SE16 ; Mukamel RE3, 17, 18 Show All Authors
Authors
  1. Yengo L1
  2. Vedantam S2, 3
  3. Marouli E4
  4. Sidorenko J1
  5. Bartell E2, 3, 5
  6. Sakaue S3, 6, 7, 8
  7. Graff M9
  8. Eliasen AU10, 11
  9. Jiang Y12
  10. Raghavan S13, 14
  11. Miao J2, 3
  12. Arias JD15
  13. Graham SE16
  14. Mukamel RE3, 17, 18
  15. Spracklen CN19, 20
  16. Yin X21
  17. Chen SH22
  18. Ferreira T23
  19. Highland HH9
  20. Ji Y24
  21. Karaderi T25, 26
  22. Lin K27
  23. Lull K28
  24. Malden DE27
  25. Medinagomez C29
  26. Machado M15
  27. Moore A30
  28. Rueger S31, 32
  29. Sim X33
  30. Vrieze S34
  31. Ahluwalia TS35, 36
  32. Akiyama M6, 37
  33. Allison MA38
  34. Alvarez M39
  35. Andersen MK40
  36. Ani A41, 42
  37. Appadurai V43
  38. Arbeeva L44
  39. Bhaskar S45
  40. Bielak LF46
  41. Bollepalli S47
  42. Bonnycastle LL48
  43. Borkjensen J40
  44. Bradfield JP49, 50
  45. Bradford Y51
  46. Braund PS52, 53
  47. Brody JA54
  48. Burgdorf KS55, 56
  49. Cade BE5, 57
  50. Cai H58
  51. Cai Q58
  52. Campbell A59
  53. Canadasgarre M60
  54. Catamo E61
  55. Chai JF33
  56. Chai X62, 63
  57. Chang LC64
  58. Chang YC64, 65, 66
  59. Chen CH64
  60. Chesi A67, 68
  61. Choi SH69
  62. Chung RH70
  63. Cocca M61
  64. Concas MP61
  65. Couture C71
  66. Cuellarpartida G12, 72
  67. Danning R73
  68. Daw EW74
  69. Degenhard F75
  70. Delgado GE76
  71. Delitala A77
  72. Demirkan A78, 79
  73. Deng X80
  74. Devineni P81
  75. Dietl A82, 83
  76. Dimitriou M84
  77. Dimitrov L85
  78. Dorajoo R86, 87
  79. Ekici AB88
  80. Engmann JE89
  81. Fairhursthunter Z27
  82. Farmaki AE84
  83. Faul JD90
  84. Fernandezlopez JC91
  85. Forer L92
  86. Francescatto M93
  87. Freitagwolf S94
  88. Fuchsberger C95
  89. Galesloot TE96
  90. Gao Y97
  91. Gao Z98, 99
  92. Geller F101
  93. Giannakopoulou O4
  94. Giulianini F73
  95. Gjesing AP40
  96. Goel A26, 102
  97. Gordon SD103
  98. Gorski M82
  99. Grove J104, 105, 106
  100. Guo X107
  101. Gustafsson S108
  102. Haessler J109
  103. Hansen TF43, 56, 110
  104. Havulinna AS47, 111
  105. Haworth SJ112, 113
  106. He J58
  107. Heardcosta N114, 115
  108. Hebbar P116
  109. Hindy G3, 117
  110. Ho YLA118
  111. Hofer E119, 120
  112. Holliday E121
  113. Horn K122, 123
  114. Hornsby WE16
  115. Hottenga JJ124
  116. Huang H125
  117. Huang J126, 127
  118. Huertachagoya A128, 129, 130
  119. Huffman JE118
  120. Hung YJ131
  121. Huo S132
  122. Hwang MY133
  123. Iha H134
  124. Ikeda DD134
  125. Isono M135
  126. Jackson AU21
  127. Jager S136, 137
  128. Jansen IE138, 139
  129. Johansson I140, 141
  130. Jonas JB142, 143, 144, 145
  131. Jonsson A40
  132. Jorgensen T146, 147
  133. Kalafati IP84
  134. Kanai M3, 6, 7
  135. Kanoni S4
  136. Karhus LL146
  137. Kasturiratne A148
  138. Katsuya T149
  139. Kawaguchi T150
  140. Kember RL151
  141. Kentistou KA152, 153
  142. Kim HN154, 155
  143. Kim YJ133
  144. Kleber ME76, 156
  145. Knol MJ78
  146. Kurbasic A157
  147. Lauzon M107
  148. Le P158, 159
  149. Lea R160
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  151. Leonard HL162, 163, 164
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  153. Li X107
  154. Li X107
  155. Liang J166
  156. Lin H167
  157. Lin SY168
  158. Liu J27, 78
  159. Liu X101
  160. Lo KS169
  161. Long J58
  162. Loresmotta L170
  163. Luan J171
  164. Lyssenko V172, 173
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  166. Mahajan A26, 498
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  168. Mangino M178, 179
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  171. Mattheisen M104, 182, 183
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  173. Mcdaid AF31, 32
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  177. Milaneschi Y187
  178. Miller JE188, 189
  179. Millwood IY190
  180. Mishra PP174, 175
  181. Mitchell RE112, 191
  182. Mollehave LT146
  183. Morgan A61
  184. Mucha S192
  185. Munz M192
  186. Nakatochi M193
  187. Nelson CP52, 53
  188. Nethander M194, 195
  189. Nho CW196
  190. Nielsen AA197
  191. Nolte IM41
  192. Nongmaithem SS45, 198
  193. Noordam R199
  194. Ntalla I4
  195. Nutile T200
  196. Pandit A21
  197. Christofidou P178
  198. Parna K28, 41
  199. Pauper M170
  200. Petersen ERB201
  201. Petersen LV105, 202
  202. Pitkanen N203, 204
  203. Polasek O205, 206
  204. Poveda A157
  205. Preuss MH207, 208
  206. Pyarajan S5, 57, 81
  207. Raffield LM19
  208. Rakugi H149
  209. Ramirez J4, 209, 210
  210. Rasheed A211
  211. Raven D212
  212. Rayner NW26, 198, 213, 214
  213. Riveros C215, 216
  214. Rohde R9
  215. Ruggiero D200, 217
  216. Ruotsalainen SE47
  217. Ryan KA218, 219
  218. Sabaterlleal M220, 221
  219. Saxena R3, 186
  220. Scholz M122, 123
  221. Sendamarai A81
  222. Shen B222
  223. Shi J12
  224. Shin JH223
  225. Sidore C224
  226. Sitlani CM54
  227. Slieker RC225, 226, 227
  228. Smit RAJ207, 228
  229. Smith AV46, 229
  230. Smith JA46, 90
  231. Smyth LJ60
  232. Southam L213, 230
  233. Steinthorsdottir V231
  234. Sun L132
  235. Takeuchi F135
  236. Tallapragada DSP45, 232
  237. Taylor KD107
  238. Tayo BO233
  239. Tcheandjieu C234, 235
  240. Terzikhan N78
  241. Tesolin P93
  242. Teumer A236, 237
  243. Theusch E238
  244. Thompson DJ239, 240
  245. Thorleifsson G231
  246. Timmers PRHJ152, 181
  247. Trompet S199, 241
  248. Turman C125
  249. Vaccargiu S224
  250. Van Der Laan SW242
  251. Van Der Most PJ41
  252. Van Klinken JB243, 244, 245
  253. Van Setten J246
  254. Verma SS67
  255. Verweij N247
  256. Veturi Y51
  257. Wang CA215, 216
  258. Wang C86, 248
  259. Wang L74
  260. Wang Z207
  261. Warren HR4, 249
  262. Bin Wei W250
  263. Wickremasinghe AR148
  264. Wielscher M251, 252
  265. Wiggins KL54
  266. Winsvold BS253, 254
  267. Wong A255
  268. Wu Y1
  269. Wuttke M256, 257
  270. Xia R258
  271. Xie T41
  272. Yamamoto K259
  273. Yang J260, 261
  274. Yao J107
  275. Young H34
  276. Yousri NA262, 263
  277. Yu L260, 261
  278. Zeng L264
  279. Zhang W265, 266
  280. Zhang X51
  281. Zhao JH267
  282. Zhao W46
  283. Zhou W3, 268, 269, 270
  284. Zimmermann ME82
  285. Zoledziewska M224
  286. Adair LS271, 272
  287. Adams HHH273, 274, 275
  288. Aguilarsalinas CA276, 277
  289. Almulla F116
  290. Arnett DK278
  291. Asselbergs FW246, 279, 280
  292. Asvold BO281, 282, 283
  293. Attia J121
  294. Banas B284
  295. Bandinelli S285
  296. Bennett DA260, 261
  297. Bergler T284
  298. Bharadwaj D286
  299. Biino G287
  300. Bisgaard H10
  301. Boerwinkle E288
  302. Boger CA284, 289, 290
  303. Bonnelykke K10
  304. Boomsma DI124
  305. Borglum AD104, 105, 291, 292
  306. Borja JB293, 294
  307. Bouchard C295
  308. Bowden DW85, 296
  309. Brandslund I297, 298
  310. Brumpton B281, 299
  311. Buring JE5, 73
  312. Caulfield MJ4, 249
  313. Chambers JC265, 266, 300, 301
  314. Chandak GR45, 302
  315. Chanock SJ15
  316. Chaturvedi N255
  317. Chen YDI107
  318. Chen Z190
  319. Cheng CY62, 303
  320. Christophersen IE304, 305
  321. Ciullo M200, 217
  322. Cole JW306, 307
  323. Collins FS48
  324. Cooper RS233
  325. Cruz M308
  326. Cucca F224, 309
  327. Cupples LA80, 115
  328. Cutler MJ310
  329. Damrauer SM51, 311, 312
  330. Dantoft TM146
  331. De Borst GJ313
  332. De Groot LCPGM314
  333. De Jager PL3, 315
  334. De Kleijn DPV313
  335. Janaka De Silva H148
  336. Dedoussis GV84
  337. Den Hollander AI170
  338. Du S271, 272
  339. Easton DF239, 316
  340. Elders PJM317
  341. Eliassen AH57, 125, 318
  342. Ellinor PT69, 319, 320
  343. Elmstahl S321
  344. Erdmann J192
  345. Evans MK222
  346. Fatkin D322, 323, 324
  347. Feenstra B101
  348. Feitosa MF74
  349. Ferrucci L325
  350. Ford I326
  351. Fornage M258, 327
  352. Franke A75
  353. Franks PW157, 318, 328
  354. Freedman BI329
  355. Gasparini P61, 93
  356. Gieger C99, 137
  357. Girotto G61, 93
  358. Goddard ME330, 331
  359. Golightly YM9, 44, 332, 333
  360. Gonzalezvillalpando C334
  361. Gordonlarsen P271, 272
  362. Grallert H99, 137
  363. Grant SFA49, 335, 336, 337
  364. Grarup N40
  365. Griffiths L160
  366. Gudnason V229, 338
  367. Haiman C339
  368. Hakonarson H49, 335, 340, 341
  369. Hansen T40
  370. Hartman CA212
  371. Hattersley AT342
  372. Hayward C181
  373. Heckbert SR343
  374. Heng CK344, 345
  375. Hengstenberg C346
  376. Hewitt AW347, 348, 349
  377. Hishigaki H134
  378. Hoyng CB170
  379. Huang PL5, 320, 350
  380. Huang W351
  381. Hunt SC262, 352
  382. Hveem K281, 282
  383. Hypponen E353, 354
  384. Iacono WG34
  385. Ichihara S355
  386. Ikram MA78
  387. Isasi CR356
  388. Jackson RD357
  389. Jarvelin MR251, 358, 359, 360
  390. Jin ZB145, 361
  391. Jockel KH184
  392. Joshi PK153
  393. Jousilahti P111
  394. Jukema JW241, 362, 363
  395. Kahonen M364, 365
  396. Kamatani Y6, 366
  397. Kang KD367
  398. Kaprio J47
  399. Kardia SLR46
  400. Karpe F214, 368
  401. Kato N135
  402. Kee F60
  403. Kessler T264, 369
  404. Khera AV3, 186
  405. Khor CC86
  406. Kiemeney LALM96, 370
  407. Kim BJ133
  408. Kim EK371, 372
  409. Kim HL373
  410. Kirchhof P374, 375, 376, 377
  411. Kivimaki M378
  412. Koh WP379
  413. Koistinen HA111, 380, 381
  414. Kolovou GD382
  415. Kooner JS265, 301, 383, 384
  416. Kooperberg C109
  417. Kottgen A256
  418. Kovacs P385
  419. Kraaijeveld A246
  420. Kraft P125
  421. Krauss RM238
  422. Kumari M386
  423. Kutalik Z31, 32
  424. Laakso M387
  425. Lange LA388
  426. Langenberg C171, 389
  427. Launer LJ222
  428. Le Marchand L390
  429. Lee H391
  430. Lee NR293
  431. Lehtimaki T174, 175
  432. Li H132
  433. Li L392, 393
  434. Lieb W394
  435. Lin X132, 395
  436. Lind L108
  437. Linneberg A146, 396
  438. Liu CT80
  439. Liu J27, 78
  440. Loeffler M122, 123
  441. London B397
  442. Lubitz SA69, 319, 320
  443. Lye SJ398
  444. Mackey DA347, 349
  445. Magi R28
  446. Magnusson PKE399
  447. Marcus GM400
  448. Vidal PM401, 402
  449. Martin NG103
  450. Marz W76, 403, 404
  451. Matsuda F150
  452. Mcgarrah RW405, 406
  453. Mcgue M34
  454. Mcknight AJ60
  455. Medland SE407
  456. Mellstrom D194, 408
  457. Metspalu A28
  458. Mitchell BD218, 219, 409
  459. Mitchell P410
  460. Mookkanamori DO228, 411
  461. Morris AD412
  462. Mucci LA125
  463. Munroe PB4, 249
  464. Nalls MA162, 163, 164
  465. Nazarian S413
  466. Nelson AE44, 414
  467. Neville MJ214, 368
  468. Newtoncheh C186, 320
  469. Nielsen CS415, 416
  470. Nothen MM417
  471. Ohlsson C194, 418
  472. Oldehinkel AJ212
  473. Orozco L419
  474. Pahkala K203, 204, 420
  475. Pajukanta P39, 421
  476. Palmer CNA422
  477. Parra EJ159
  478. Pattaro C95
  479. Pedersen O40
  480. Pennell CE215, 216
  481. Penninx BWJH187
  482. Perusse L71, 423
  483. Peters A100, 137, 424
  484. Peyser PA46
  485. Porteous DJ59
  486. Posthuma D138
  487. Power C425
  488. Pramstaller PP95
  489. Province MA74
  490. Qi Q356
  491. Qu J361
  492. Rader DJ51, 426
  493. Raitakari OT203, 204, 427
  494. Ralhan S428
  495. Rallidis LS429
  496. Rao DC430
  497. Redline S5, 57
  498. Reilly DF431
  499. Reiner AP109, 432
  500. Rhee SY433
  501. Ridker PM5, 73
  502. Rienstra M247
  503. Ripatti S3, 47, 434
  504. Ritchie MD51
  505. Roden DM435
  506. Rosendaal FR228
  507. Rotter JI107
  508. Rudan I152
  509. Rutters F436
  510. Sabanayagam C62, 303
  511. Saleheen D211, 437
  512. Salomaa V111
  513. Samani NJ52, 53
  514. Sanghera DK438, 439, 440, 441
  515. Sattar N442
  516. Schmidt B184
  517. Schmidt H443
  518. Schmidt R119
  519. Schulze MB136, 137, 444
  520. Schunkert H445
  521. Scott LJ21
  522. Scott RJ446
  523. Sever P384
  524. Shiroma EJ222
  525. Shoemaker MB447
  526. Shu XO58
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  528. Sims M97
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  532. Smith JG450, 451, 452
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  536. Stark KJ82
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  548. Tusieluna MT461, 462
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  554. Van Schoor NM466
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  570. Willett WC125, 318
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  582. Zheng W58
  583. Zhu X166
  584. Zmuda JM478
  585. Zonderman AB222
  586. Zwart JA253, 480
  587. Partida GC12
  588. Sun Y484, 485
  589. Croteauchonka D57
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  591. Chasman DI5, 73
  592. Cho YS223
  593. Heid IM82
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Source: Nature Published:2022


Abstract

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40–50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10–20% (14–24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries. © 2022, The Author(s).
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