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

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tm-ar-pimphen-2015.pdf (1.06 MB)

Accepted Date

2014-10-27

Issued Date

2015-03-06

Copyright Date

2015

Resource Type

Article

Language

eng

ISSN

2041-1723 (electronic)

DOI

10.1038/ncomms6681.

Rights Holder(s)

Nature communications

Bibliographic Citation

Taylor PN, Porcu E, Chew S, Campbell PJ, Traglia M, Brown SJ. et al. Whole-genome sequence-based analysis of thyroid function. Nat Commun. 2015 Mar 6;6:5681.

Suggested Citation

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., Pimphen Charoen, พิมพ์เพ็ญ เจริญ, 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, Smith, George Davey, Durbin, Richard, Richards, J. Brent, Sanna, Serena, Soranzo, Nicole, Timpson, Nicholas J., Wilson, Scott G. Whole-genome sequence-based analysis of thyroid function.. Taylor PN, Porcu E, Chew S, Campbell PJ, Traglia M, Brown SJ. et al. Whole-genome sequence-based analysis of thyroid function. Nat Commun. 2015 Mar 6;6:5681.. doi:10.1038/ncomms6681. Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/803

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Title

Whole-genome sequence-based analysis of thyroid function.

Author(s)

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.
 Pimphen Charoen
 พิมพ์เพ็ญ เจริญ
 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
 Smith, George Davey
 Durbin, Richard
 Richards, J. Brent
 Sanna, Serena
 Soranzo, Nicole
 Timpson, Nicholas J.
 Wilson, Scott G.

Corresponding Author(s)

Taylor, Peter N.
 Wilson, Scott G.

Other Contributor(s)

Mahidol University. Faculty of Tropical Medicine. Department of Tropical Hygiene

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.

Keyword(s)

Sequence-based
 Thyroid
 Whole-genome
 Open Access article

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/803

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