Publication:
Whole-genome sequence-based analysis of thyroid function

Issued Date

2015-01-01

Resource Type

Article

ISSN

20411723

DOI

10.1038/ncomms6681

Other identifier(s)

2-s2.0-84924347503

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

Nature Communications. Vol.6, (2015)

Suggested Citation

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 Whole-genome sequence-based analysis of thyroid function. Nature Communications. Vol.6, (2015). doi:10.1038/ncomms6681 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/35655

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Title

Whole-genome sequence-based analysis of thyroid function

Author(s)

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

Other Contributor(s)

Cardiff University
 Consiglio Nazionale delle Ricerche
 Universita degli Studi di Sassari
 University of Michigan, Ann Arbor
 Sir Charles Gairdner Hospital
 IRCCS San Raffaele Scientific Institute
 University of Western Australia
 University of Bristol
 Wellcome Trust
 Barts and The London School of Medicine and Dentistry
 PathWest Laboratory Medicine WA
 London School of Hygiene & Tropical Medicine
 Mahidol University
 Lady Davis Institute for Medical Research
 McGill University
 National Heart
 Addenbrooke's Hospital
 King's College London
 NIA
 IFB Halle GmbH
 King Abdulaziz Medical City- Riyadh
 Trinity College Dublin
 UCL Institute of Child Health
 Queen's University, Kingston
 University of Cambridge
 Wellcome Trust Centre for Human Genetics
 University of Edinburgh
 Cambridge Institute for Medical Research
 UCL
 Institut für Humangenetik
 Eli Lilly and Company
 NHS Foundation Trust
 University of Sussex
 Biogen Inc.
 BGI-Shenzhen
 University of Queensland
 Edinburgh Medical School, Medical Research Council Human Genetics Unit
 Queen Mary, University of London

Abstract

© 2015 Macmillan Publishers Limited. All rights reserved. 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.

Keyword(s)

Biochemistry, Genetics and Molecular Biology
 Chemistry

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/35655

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Scopus 2011-2015