Whole-genome sequence-based analysis of thyroid function

著者: Peter Taylor, Eleonora Porcu, Shelby Chew, Purdey J. Campbell, Michela Traglia, Suzanne J. Brown, Benjamin H. Mullin, Hashem A. Shihab, Josine L. Min, Klaudia Walter, Yasin Memari, Jie Huang, Michael R. Barnes, John Beilby, Pimphen Charoen, Petr Danecek, Frank Dudbridge, Vincenzo Forgetta, Celia M.T. Greenwood, Elin Grundberg, Andrew D. Johnson, Jennie Hui, Ee Mun Lim, Shane McCarthy, Dawn Muddyman, Vijay Panicker, John R. B. Perry, Jordana T. Bell, Wei Yuan, Caroline L. Relton, Tom R. Gaunt, David Schlessinger, Gonçalo R. Abecasis, Francesco Cucca, Gabriela Surdulescu, Wolfram Woltersdorf, Eleftheria Zeggini, Hou‐Feng Zheng, Daniela Toniolo, Colin Dayan, Silvia Naitza, John P. Walsh, Tim D. Spector, George Davey Smith, Richard Durbin, J. Brent Richards, Serena Sanna, Nicole Soranzo, Nicholas J. Timpson, Scott G. Wilson, Saeed Al Turki, Carl A. Anderson, Richard Anney, Dinu Antony, María Soler Artigas, Muhammad Ayub, Senduran Balasubramaniam, Jeffrey C. Barrett, Inês Barroso, Phil Beales, Jamie Bentham, Shoumo Bhattacharya, Ewan Birney, Douglas Blackwood, Martin Bobrow, Elena G. Bochukova, Patrick Bolton, Rebecca Bounds, Chris Boustred, Gerome Breen, Mattia Calissano, Keren Carss, Krishna Chatterjee, Lu Chen, Antonio Ciampi, Sebhattin Cirak, Peter Clapham, Gail Clement, Guy Coates, David Collier, Catherine Cosgrove, Tony Cox, Nick Craddock, Lucy Crooks, Sarah Curran, David Curtis, Allan Daly, Aaron Day-Williams, Ian N. M. Day, Thomas A. Down, Yuanping Du, Ian Dunham, Sarah Edkins, Peter Ellis, David M. Evans, Sadaf Faroogi, Ghazaleh Fatemifar, David Fitzpatrick, Paul Flicek, James Flyod, A. Reghan Foley, Christopher S. Franklin, Marta Futema, Louise Gallagher, Matthias Geihs, Daniel Geschwind, Heather Griffin, Detelina Grozeva, Xueqin Guo, Xiaosen Guo, Hugh Gurling, Deborah Hart, Audrey E. Hendricks, Peter Holmans, Bryan Howie, Liren Huang, Tim Hubbard, Steve E. Humphries, Matthew E. Hurles, Pirro G. Hysi, David K. Jackson, Yalda Jamshidi, Jing Tian, Christopher Joyce, Jane Kaye, Thomas Keane, Julia M. Keogh, John P. Kemp, Karen Kennedy, Anja Kolb-Kokocinski, Geneviève Lachance, Cordelia Langford, Daniel Lawson, Irene Lee, Monkol Lek, Jieqin Liang, Honghuang Lin, Rui Li, Rui Li, Ryan Liu, Jouko Lönnqvist, Margarida Lopes, Valentina Iotchkova, Daniel G. MacArthur, Jonathan Marchini, John Maslen, Mangino Massimo, Iain Mathieson, Gaëlle Marenne, Peter McGuffin, Andrew M. McIntosh, Andrew G. McKechanie, Andrew McQuillin, Sarah Metrustry, Hannah M. Mitchison, Alireza Moayyeri, James Morris, Francesco Muntoni, Kate Northstone, Michael O'Donnovan, Alexandros Onoufriadis, Stephen O’Rahilly, Karim Oualkacha, Michael J. Owen, Aarno Palotie, Kalliope Panoutsopoulou, Victoria Parker, Jeremy Parr, Lavinia Paternoster, Tiina Paunio, Felicity Payne, Olli Pietiläinen, Vincent Plagnol, Lydia Quaye, Michael A. Quail, Lucy Raymond, Karola Rehnström, Susan M. Ring, Graham R. S. Ritchie, Nicola D. Roberts, David B. Savage, Peter Scambler, Stephen Schiffels, Miriam Schmidts, Nadia Schoenmakers, Robert K. Semple, Eva Serra, Sally I. Sharp, So-Youn Shin, David Skuse, Kerrin S. Small, Lorraine Southam, Olivera Spasić-Bošković, David St Clair, Jim Stalker, Elizabeth Stevens, Beate St Pourcian, Jianping Sun, Jaana Suvisaari, Ionna Tachmazidou, Martin D. Tobin, Ana M. Valdes, Margriet van Kogelenberg, Parthiban Vijayarangakannan, Peter M. Visscher, Louise V. Wain, James Walters, Guangbiao Wang, Jun Wang, Yu Wang, Kirsten Ward, Elanor Wheeler, Tamieka Whyte, Hywel Williams, Kathleen A. Williamson, Crispian Wilson, Kim Wong, Changjiang Xu, Jian Yang, F. Zhang, Pingbo Zhang - Nature Communications 2015 被引用: 107

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.