Whole-genome sequence-based analysis of thyroid function

Taylor, Peter N, Porcu, Eleonora, Chew, Shelby, Campbell, Purdey J, Traglia, Michela, Brown, Suzanne J, Mullin, Benjamin H, Shihab, Hashem A, Min, Josine, Walter, Klaudia, Memari, Yasin, Huang, Jie, Barnes, Michael R, Beilby, John P, Charoen, Pimphen, Danecek, Petr, Dudbridge, Frank, Forgetta, Vincenzo, Greenwood, Celia, Grundberg, Elin, Johnson, Andrew D, Hui, Jennie, Lim, Ee M, McCarthy, Shane, Muddyman, Dawn, Panicker, Vijay, Perry, John R B, Bell, Jordana T, Yuan, Wei, Relton, Caroline, Gaunt, Tom, Schlessinger, David, Abecasis, Goncalo, Cucca, Francesco, Surdulescu, Gabriela L, Woltersdorf, Wolfram, Zeggini, Eleftheria, Zheng, Hou-Feng, Toniolo, Daniela, Dayan, Colin M, Naitza, Silvia, Walsh, John P, Spector, Tim, Davey Smith, George, Durbin, Richard, Brent Richards, J, Sanna, Serena, Soranzo, Nicole, Timpson, Nicholas J, Wilson, Scott G, Turki, Saeed Al, Anderson, Carl, Anney, Richard, Antony, Dinu, Artigas, Maria Soler, Ayub, Muhammad, Balasubramaniam, Senduran, Barrett, Jeffrey C, Barroso, Inês, Beales, Phil, Bentham, Jamie, Bhattacharya, Shoumo, Birney, Ewan, Blackwood, Douglas, Bobrow, Martin, Bochukova, Elena, Bolton, Patrick, Bounds, Rebecca, Boustred, Chris, Breen, Gerome, Calissano, Mattia, Carss, Keren, Chatterjee, Krishna, Chen, Lu, Ciampi, Antonio, Cirak, Sebhattin, Clapham, Peter, Clement, Gail, Coates, Guy, Collier, David, Cosgrove, Catherine, Cox, Tony, Craddock, Nick, Crooks, Lucy, Curran, Sarah, Curtis, David, Daly, Allan, Day-Williams, Aaron, Day, Ian N M, Down, Thomas, Du, Yuanping, Dunham, Ian, Edkins, Sarah, Ellis, Peter, Evans, David, Faroogi, Sadaf, Fatemifar, Ghazaleh, Fitzpatrick, David R, Flicek, Paul, Flyod, James, Foley, A. Reghan, Franklin, Christopher S, Futema, Marta, Gallagher, Louise, Geihs, Matthias, Geschwind, Daniel, Griffin, Heather, Grozeva, Detelina, Guo, Xueqin, Guo, Xiaosen, Gurling, Hugh, Hart, Deborah, Hendricks, Audrey, Holmans, Peter, Howie, Bryan, Huang, Liren, Hubbard, Tim, Humphries, Steve E, Hurles, Matthew E, Hysi, Pirro, Jackson, David K, Jamshidi, Yalda, Jing, Tian, Joyce, Chris, Kaye, Jane, Keane, Thomas, Keogh, Julia, Kemp, John, Kennedy, Karen, Kolb-Kokocinski, Anja, Lachance, Genevieve, Langford, Cordelia, Lawson, Daniel, Lee, Irene, Lek, Monkol, Liang, Jieqin, Lin, Hong, Li, Rui, Li, Yingrui, Liu, Ryan, Lönnqvist, Jouko, Lopes, Margarida, Lotchkova, Valentina, MacArthur, Daniel, Marchini, Jonathan, Maslen, John, Massimo, Mangino, Mathieson, Iain, Marenne, Gaëlle, McGuffin, Peter, McIntosh, Andrew, McKechanie, Andrew G, McQuillin, Andrew, Metrustry, Sarah, Mitchison, Hannah, Moayyeri, Alireza, Morris, James, Muntoni, Francesco, Northstone, Kate, O'Donnovan, Michael, Onoufriadis, Alexandros, O'Rahilly, Stephen, Oualkacha, Karim, Owen, Michael J, Palotie, Aarno, Panoutsopoulou, Kalliope, Parker, Victoria, Parr, Jeremy R, Paternoster, Lavinia, Paunio, Tiina, Payne, Felicity, Pietilainen, Olli, Plagnol, Vincent, Quaye, Lydia, Quai, Michael A, Raymond, Lucy, Rehnström, Karola, Richards, Brent, Ring, Susan, Ritchie, Graham R S, Roberts, Nicola, Savage, David B, Scambler, Peter, Schiffels, Stephen, Schmidts, Miriam, Schoenmakers, Nadia, Semple, Robert K, Serra, Eva, Sharp, Sally I, Shin, So-Youn, Skuse, David, Small, Kerrin, Southam, Lorraine, Spasic-Boskovic, Olivera, Clair, David St, Stalker, Jim, Stevens, Elizabeth, Pourcian, Beate St, Sun, Jianping, Suvisaari, Jaana, Tachmazidou, Ionna, Tobin, Martin D, Valdes, Ana, Kogelenberg, Margriet Van, Vijayarangakannan, Parthiban, Visscher, Peter M, Wain, Louise V, Walters, James T R, Wang, Guangbiao, Wang, Jun, Wang, Yu, Ward, Kirsten, Wheeler, Elanor, Whyte, Tamieka, Williams, Hywel, Williamson, Kathleen A, Wilson, Crispian, Wong, Kim, Xu, ChangJiang, Yang, Jian, Zhang, Fend and Zhang, Pingbo (2015) Whole-genome sequence-based analysis of thyroid function. Nature Communications, 6 (5681). ISSN 2041-1723

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Abstract

Normal thyroid function is essential for health, but its genetic architecture remains poorly understood. Here, for the heritable thyroid traits thyrotropin (TSH) and free ​thyroxine (FT4), we analyse whole-genome sequence data from the UK10K project (N=2,287). Using additional whole-genome sequence and deeply imputed data sets, we report meta-analysis results for common variants (MAF≥1%) associated with TSH and FT4 (N=16,335). For TSH, we identify a novel variant in ​SYN2 (MAF=23.5%, P=6.15 × 10−9) and a new independent variant in ​PDE8B (MAF=10.4%, P=5.94 × 10−14). For FT4, we report a low-frequency variant near ​B4GALT6/​SLC25A52 (MAF=3.2%, P=1.27 × 10−9) tagging a rare ​TTR variant (MAF=0.4%, P=2.14 × 10−11). All common variants explain ≥20% of the variance in TSH and FT4. Analysis of rare variants (MAF<1%) using sequence kernel association testing reveals a novel association with FT4 in ​NRG1. Our results demonstrate that increased coverage in whole-genome sequence association studies identifies novel variants associated with thyroid function.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Brighton and Sussex Medical School
Depositing User: Nikoleta Kiapidou
Date Deposited: 07 Jul 2015 06:28
Last Modified: 12 Mar 2017 03:57
URI: http://sro.sussex.ac.uk/id/eprint/55159

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