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Whole-genome sequence-based analysis of thyroid function

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posted on 2023-06-08, 21:26 authored by Peter N Taylor, Eleonora Porcu, Shelby Chew, Purdey J Campbell, Michela Traglia, Suzanne J Brown, Benjamin H Mullin, Hashem A Shihab, Josine Min, Klaudia Walter, Yasin Memari, Jie Huang, Michael R Barnes, John P Beilby, Pimphen Charoen, Petr Danecek, Frank Dudbridge, Vincenzo Forgetta, Celia Greenwood, Elin Grundberg, Andrew D Johnson, Jennie Hui, Ee M Lim, Shane McCarthy, Dawn Muddyman, Vijay Panicker, John R B Perry, Jordana T Bell, Wei Yuan, Caroline Relton, Tom Gaunt, David Schlessinger, Goncalo Abecasis, Francesco Cucca, Gabriela L Surdulescu, Wolfram Woltersdorf, Eleftheria Zeggini, Hou-Feng Zheng, Daniela Toniolo, Colin M Dayan, Silvia Naitza, John P Walsh, Tim Spector, George Davey Smith, Richard Durbin, J Brent Richards, Serena Sanna, Nicole Soranzo, Nicholas J Timpson, Scott G Wilson, Saeed Al Turki, Carl Anderson, Richard Anney, Dinu Antony, Maria Soler Artigas, Muhammad Ayub, Senduran Balasubramaniam, Jeffrey C Barrett, Inês Barroso, Phil Beales, Jamie Bentham, Shoumo Bhattacharya, Ewan Birney, Douglas Blackwood, Martin Bobrow, Elena 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 Down, Yuanping Du, Ian Dunham, Sarah Edkins, Peter Ellis, David Evans, Sadaf Faroogi, Ghazaleh Fatemifar, David R 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 Hendricks, Peter Holmans, Bryan Howie, Liren Huang, Tim Hubbard, Steve E Humphries, Matthew E Hurles, Pirro Hysi, David K Jackson, Yalda Jamshidi, Tian Jing, Chris Joyce, Jane Kaye, Thomas Keane, Julia Keogh, John Kemp, Karen Kennedy, Anja Kolb-Kokocinski, Genevieve Lachance, Cordelia Langford, Daniel Lawson, Irene Lee, Monkol Lek, Jieqin Liang, Hong Lin, Rui Li, Yingrui Li, Ryan Liu, Jouko Lönnqvist, Margarida Lopes, Valentina Lotchkova, Daniel MacArthur, Jonathan Marchini, John Maslen, Mangino Massimo, Iain Mathieson, Gaëlle Marenne, Peter McGuffin, Andrew McIntosh, Andrew G McKechanie, Andrew McQuillin, Sarah Metrustry, Hannah 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 R Parr, Lavinia Paternoster, Tiina Paunio, Felicity Payne, Olli Pietilainen, Vincent Plagnol, Lydia Quaye, Michael A Quai, Lucy Raymond, Karola Rehnström, Brent Richards, Susan Ring, Graham R S Ritchie, Nicola 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 Small, Lorraine Southam, Olivera Spasic-Boskovic, David St Clair, Jim Stalker, Elizabeth Stevens, Beate St Pourcian, Jianping Sun, Jaana Suvisaari, Ionna Tachmazidou, Martin D Tobin, Ana Valdes, Margriet Van Kogelenberg, Parthiban Vijayarangakannan, Peter M Visscher, Louise V Wain, James T R 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, Fend Zhang, Pingbo Zhang
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.

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Publication status

  • Published

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  • Published version

Journal

Nature Communications

ISSN

2041-1723

Publisher

Nature

Issue

5681

Volume

6

Department affiliated with

  • BSMS Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2015-07-07

First Open Access (FOA) Date

2015-07-07

First Compliant Deposit (FCD) Date

2015-07-07

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