Whole-genome sequence-based analysis of thyroid function

Mccarthy, Shane; Taylor, Peter N.; Brown, Suzanne J.; Porcu, Eleonora; Campbell, Purdey J.; Chew, Shelby; Al Turki, Saeed; Mullin, Benjamin H.; Soler Artigas, Maria; Wilson, Scott G.; Pn, Taylor; Shihab, Hashem A.; Traglia, Michela; Turki, Saeed Al; Anderson, Carl A.; Bell, Jordana T.; Anney, Richard J. L.; Richards, J. B.; Barnes, Michael R.; Antony, Dinu; Artigas, Maria Soler; Ayub, Muhammad K.; Beilby, John P.; Balasubramaniam, Senduran; Min, Josine; Barrett, Jeffrey C.; Charoen, Pimphen; Barroso, Inês; Breen, Gerome; Beales, Phil L.; Danecek, Petr; Bentham, Jamie R.; Bhattacharya, Shoumo; Dudbridge, Frank; Birney, Ewan; Blackwood, Douglas H. R.; Forgetta, Vincenzo; Walter, Klaudia K. H.; Bobrow, Martin N.; Bochukova, Elena G.; Memari, Yasin; Greenwood, Celia; Bolton, Patrick A.; Bounds, Rebecca; Boustred, Chris R.; Grundberg, Elin; Huang, Jie; Johnson, Andrew D.; Calissano, Mattia; Carss, Keren J.; Hui, Jennie; Chatterjee, Krishna; Chen, Lu; Lim, Ee Mun; Ciampi, Antonio; Cirak, Sebhattin; Pj, Campbell; Yuan, Wei; Clapham, Peter; Muddyman, Dawn; Clement, Gail; Panicker, Vijay; Coates, Guy; Collier, David A.; Walters, James T. R.; Perry, John R. B.; Cosgrove, Catherine L.; Cox, Tony V.; Craddock, Nick J.; Crooks, Lucy; Curran, Sarah R.; Curtis, David; Daly, Allan; Day-Williams, Aaron G.; Day, Ian N. M.; Relton, Caroline L.; Down, Thomas A.; Woltersdorf, Wolfram; Du, Yuanping; Dunham, Ian; Zeggini, Eleftheria; Gaunt, Tom R.; Edkins, Sarah J.; Ellis, Peter D.; Evans, David M. D.; Faroogi, Sadaf; Zheng, Hou-Feng; Fatemifar, Ghazaleh; Schlessinger, David; Fitzpatrick, David R.; Flicek, Paul; Foley, A. Reghan; Reghan Foley, A.; Abecasis, Gonçalo R.; Flyod, James; Franklin, Christopher S.; Futema, Marta; Sj, Brown; Cucca, Francesco; Gallagher, Louise; Geihs, Matthias; Wang, Guangbiao; Surdulescu, Gabriela L.; Geschwind, Daniel H.; Wang, Jun; Griffin, Heather; Wang, Yu; Ward, Kirsten J.; McCarthy, Shane A.; Grozeva, Detelina; Wheeler, Elanor; Guo, Xiaosen; Whyte, Tamieka; Williams, Hywel; Gurling, Hugh M. D.; Guo, Xueqin; Williamson, Kathleen A.; Toniolo, Daniela; Hart, Deborah J.; Wilson, Crispian; Hendricks, Audrey E.; Dayan, Colin M.; Wong, Kim; Holmans, Peter A.; Xu, ChangJiang; Yang, Jian; Howie, Bryan N.; Naitza, Silvia; Zhang, Fend; Zhang, Pingbo; Jt, Bell; Huang, Liren; Hubbard, Tim J. P.; Walsh, John P.; Humphries, Steve E.; Bh, Mullin; Hurles, Matthew E.; Wain, Louise V.; Hysi, Pirro G.; Jackson, David K.; Spector, Tim D.; Jamshidi, Yalda; Jing, Tian; Smith, George Davey; Joyce, Chris; Davey Smith, George; Kaye, Jane; Keane, Thomas M.; Ha, Shihab; Durbin, Richard M.; Keogh, Julia M.; Kemp, John P.; Kennedy, Karen L.; Kolb-Kokocinski, Anja; Lachance, Genevieve; Langford, Cordelia; Lawson, Daniel J.; Lee, Irene; Sanna, Serena; Lek, Monkol; Liang, Jieqin; Lin, Hong; Li, Rui; Soranzo, Nicole; Li, Yingrui; Liu, Ryan; Lönnqvist, Jouko; Lopes, Margarida C.; Timpson, Nicholas J.; Lotchkova, Valentina; Mcguffin, P. W.; Macarthur, Daniel G.; Mcintosh, A. M.; Marchini, Jonathan L.; Mckechanie, A. G.; Maslen, John; Mcquillin, A.; Massimo, Mangino; Lonnqvist, Jouko; Brent Richards, J.; Mathieson, Iain; Marenne, Gaëlle; Metrustry, Sarah J.; Mitchison, Hannah M.; Moayyeri, Alireza; McGuffin, Peter; Morris, James A.; McIntosh, Andrew; Muntoni, Francesco M.; McKechanie, Andrew G.; Northstone, Kate; McQuillin, Andrew; O'Donnovan, Michael; Onoufriadis, Alexandros; O'Rahilly, Stephen P.; Oualkacha, Karim; Owen, Michael J.; Palotie, Aarno; Panoutsopoulou, Kalliope; Parker, Victoria; Parr, Jeremy R.; Paternoster, Lavinia; Quail, M. A.; Paunio, Tiina; Payne, Felicity; Pietilainen, Olli P. H.; Plagnol, Vincent; Quaye, Lydia; Raymond, Lucy F.; Rehnström, Karola; Richards, J. Brent; Ring, Susan M.; Ritchie, Graham R. S.; Quai, Michael A.; Roberts, Nicola Y.; Savage, David B.; Scambler, Peter J.; Schiffels, Stephen; Schmidts, Miriam; Schoenmakers, Nadia A.; Semple, Robert K.; Serra, Eva; Sharp, Sally I.; Shin, So-Youn; Skuse, David H.; Small, Kerrin S.; Southam, Lorraine; St Clair, David; Spasic-Boskovic, Olivera; Stalker, Jim W.; Mr, Barnes; Clair, David St; Stevens, Elizabeth; Sun, Jianping; Suvisaari, Jaana M.; Tachmazidou, Ionna; Pourcian, Beate St; Tobin, Martin D.; St Pourcian, Beate; Valdes, Ana A.; Van Kogelenberg, Margriet; Vijayarangakannan, Parthiban; Visscher, Peter M.; Jp, Beilby; Kogelenberg, Margriet Van; Uk10k, Consortium; Consortium, U. K. K.; Uk0k, Consortium; Wilson, Scott

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Scott Wilson
Mccarthy et al., 2015

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Nature Research, Nature Communications, 1(6), 2015

DOI: 10.1038/ncomms6681

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@article{Mccarthy2015,
 abstract = {AbstractNormal 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&lt;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.},
 author = {Mccarthy, Shane and Taylor, Peter N. and Brown, Suzanne J. and Porcu, Eleonora and Campbell, Purdey J. and Chew, Shelby and Al Turki, Saeed and Mullin, Benjamin H. and Soler Artigas, Maria and Wilson, Scott G. and Pn, Taylor and Shihab, Hashem A. and Traglia, Michela and Turki, Saeed Al and Anderson, Carl A. and Bell, Jordana T. and Anney, Richard J. L. and Richards, J. B. and Barnes, Michael R. and Antony, Dinu and Artigas, Maria Soler and Ayub, Muhammad K. and Beilby, John P. and Balasubramaniam, Senduran and Min, Josine and Barrett, Jeffrey C. and Charoen, Pimphen and Barroso, Inês and Breen, Gerome and Beales, Phil L. and Danecek, Petr and Bentham, Jamie R. and Bhattacharya, Shoumo and Dudbridge, Frank and Birney, Ewan and Blackwood, Douglas H. R. and Forgetta, Vincenzo and Walter, Klaudia K. H. and Bobrow, Martin N. and Bochukova, Elena G. and Memari, Yasin and Greenwood, Celia and Bolton, Patrick A. and Bounds, Rebecca and Boustred, Chris R. and Grundberg, Elin and Huang, Jie and Johnson, Andrew D. and Calissano, Mattia and Carss, Keren J. and Hui, Jennie and Chatterjee, Krishna and Chen, Lu and Lim, Ee Mun and Ciampi, Antonio and Cirak, Sebhattin and Pj, Campbell and Yuan, Wei and Clapham, Peter and Muddyman, Dawn and Clement, Gail and Panicker, Vijay and Coates, Guy and Collier, David A. and Walters, James T. R. and Perry, John R. B. and Cosgrove, Catherine L. and Cox, Tony V. and Craddock, Nick J. and Crooks, Lucy and Curran, Sarah R. and Curtis, David and Daly, Allan and Day-Williams, Aaron G. and Day, Ian N. M. and Relton, Caroline L. and Down, Thomas A. and Woltersdorf, Wolfram and Du, Yuanping and Dunham, Ian and Zeggini, Eleftheria and Gaunt, Tom R. and Edkins, Sarah J. and Ellis, Peter D. and Evans, David M. D. and Faroogi, Sadaf and Zheng, Hou-Feng and Fatemifar, Ghazaleh and Schlessinger, David and Fitzpatrick, David R. and Flicek, Paul and Foley, A. Reghan and Reghan Foley, A. and Abecasis, Gonçalo R. and Flyod, James and Franklin, Christopher S. and Futema, Marta and Sj, Brown and Cucca, Francesco and Gallagher, Louise and Geihs, Matthias and Wang, Guangbiao and Surdulescu, Gabriela L. and Geschwind, Daniel H. and Wang, Jun and Griffin, Heather and Wang, Yu and Ward, Kirsten J. and McCarthy, Shane A. and Grozeva, Detelina and Wheeler, Elanor and Guo, Xiaosen and Whyte, Tamieka and Williams, Hywel and Gurling, Hugh M. D. and Guo, Xueqin and Williamson, Kathleen A. and Toniolo, Daniela and Hart, Deborah J. and Wilson, Crispian and Hendricks, Audrey E. and Dayan, Colin M. and Wong, Kim and Holmans, Peter A. and Xu, ChangJiang and Yang, Jian and Howie, Bryan N. and Naitza, Silvia and Zhang, Fend and Zhang, Pingbo and Jt, Bell and Huang, Liren and Hubbard, Tim J. P. and Walsh, John P. and Humphries, Steve E. and Bh, Mullin and Hurles, Matthew E. and Wain, Louise V. and Hysi, Pirro G. and Jackson, David K. and Spector, Tim D. and Jamshidi, Yalda and Jing, Tian and Smith, George Davey and Joyce, Chris and Davey Smith, George and Kaye, Jane and Keane, Thomas M. and Ha, Shihab and Durbin, Richard M. and Keogh, Julia M. and Kemp, John P. and Kennedy, Karen L. and Kolb-Kokocinski, Anja and Lachance, Genevieve and Langford, Cordelia and Lawson, Daniel J. and Lee, Irene and Sanna, Serena and Lek, Monkol and Liang, Jieqin and Lin, Hong and Li, Rui and Soranzo, Nicole and Li, Yingrui and Liu, Ryan and Lönnqvist, Jouko and Lopes, Margarida C. and Timpson, Nicholas J. and Lotchkova, Valentina and Mcguffin, P. W. and Macarthur, Daniel G. and Mcintosh, A. M. and Marchini, Jonathan L. and Mckechanie, A. G. and Maslen, John and Mcquillin, A. and Massimo, Mangino and Lonnqvist, Jouko and Brent Richards, J. and Mathieson, Iain and Marenne, Gaëlle and Metrustry, Sarah J. and Mitchison, Hannah M. and Moayyeri, Alireza and McGuffin, Peter and Morris, James A. and McIntosh, Andrew and Muntoni, Francesco M. and McKechanie, Andrew G. and Northstone, Kate and McQuillin, Andrew and O'Donnovan, Michael and Onoufriadis, Alexandros and O'Rahilly, Stephen P. and Oualkacha, Karim and Owen, Michael J. and Palotie, Aarno and Panoutsopoulou, Kalliope and Parker, Victoria and Parr, Jeremy R. and Paternoster, Lavinia and Quail, M. A. and Paunio, Tiina and Payne, Felicity and Pietilainen, Olli P. H. and Plagnol, Vincent and Quaye, Lydia and Raymond, Lucy F. and Rehnström, Karola and Richards, J. Brent and Ring, Susan M. and Ritchie, Graham R. S. and Quai, Michael A. and Roberts, Nicola Y. and Savage, David B. and Scambler, Peter J. and Schiffels, Stephen and Schmidts, Miriam and Schoenmakers, Nadia A. and Semple, Robert K. and Serra, Eva and Sharp, Sally I. and Shin, So-Youn and Skuse, David H. and Small, Kerrin S. and Southam, Lorraine and St Clair, David and Spasic-Boskovic, Olivera and Stalker, Jim W. and Mr, Barnes and Clair, David St and Stevens, Elizabeth and Sun, Jianping and Suvisaari, Jaana M. and Tachmazidou, Ionna and Pourcian, Beate St and Tobin, Martin D. and St Pourcian, Beate and Valdes, Ana A. and Van Kogelenberg, Margriet and Vijayarangakannan, Parthiban and Visscher, Peter M. and Jp, Beilby and Kogelenberg, Margriet Van and Uk10k, Consortium and Consortium, U. K. K. and Uk0k, Consortium and Wilson, Scott},
 doi = {10.1038/ncomms6681},
 journal = {Nature Communications},
 month = {mar},
 title = {Whole-genome sequence-based analysis of thyroid function},
 url = {https://www.nature.com/articles/ncomms6681.pdf},
 volume = {6},
 year = {2015}
}

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Whole-genome sequence-based analysis of thyroid function

Journal article published in 2015 by Shane Mccarthy, Peter N. Taylor, Suzanne J. Brown, Eleonora Porcu, Purdey J. Campbell, Shelby Chew, Saeed Al Turki, Benjamin H. Mullin, Maria Soler Artigas, Scott G. Wilson

, Taylor Pn, Hashem A. Shihab, Michela Traglia, Saeed Al Turki, Carl A. Anderson and other authors. Shane Mccarthy, Peter N. Taylor, Suzanne J. Brown, Eleonora Porcu, Purdey J. Campbell, Shelby Chew, Saeed Al Turki, Benjamin H. Mullin, Maria Soler Artigas, Scott G. Wilson

, Taylor Pn, Hashem A. Shihab, Michela Traglia, Saeed Al Turki, Carl A. Anderson, Jordana T. Bell, Richard J. L. Anney, J. B. Richards, Michael R. Barnes

, Dinu Antony, Maria Soler Artigas, Muhammad K. Ayub, John P. Beilby, Senduran Balasubramaniam, Josine Min, Jeffrey C. Barrett, Pimphen Charoen, Inês Barroso, Gerome Breen, Phil L. Beales, Petr Danecek, Jamie R. Bentham, Shoumo Bhattacharya, Frank Dudbridge, Ewan Birney

, Douglas H. R. Blackwood, Vincenzo Forgetta

, Klaudia K. H. Walter, Martin N. Bobrow, Elena G. Bochukova, Yasin Memari, Celia Greenwood, Patrick A. Bolton, Rebecca Bounds, Chris R. Boustred, Elin Grundberg, Jie Huang, Andrew D. Johnson, Mattia Calissano, Keren J. Carss, Jennie Hui, Krishna Chatterjee, Lu Chen, Ee Mun Lim, Antonio Ciampi, Sebhattin Cirak, Campbell Pj, Wei Yuan, Peter Clapham, Dawn Muddyman, Gail Clement, Vijay Panicker

, Guy Coates, David A. Collier, James T. R. Walters, John R. B. Perry, Catherine L. Cosgrove, Tony V. Cox, Nick J. Craddock, Lucy Crooks, Sarah R. Curran, David Curtis, Allan Daly, Aaron G. Day-Williams, Ian N. M. Day, Caroline L. Relton, Thomas A. Down, Wolfram Woltersdorf, Yuanping Du, Ian Dunham

, Eleftheria Zeggini

, Tom R. Gaunt

, Sarah J. Edkins, Peter D. Ellis, David M. D. Evans, Sadaf Faroogi, Hou-Feng Zheng, Ghazaleh Fatemifar, David Schlessinger, David R. Fitzpatrick, Paul Flicek, A. Reghan Foley, A. Reghan Foley, Gonçalo R. Abecasis, James Flyod, Christopher S. Franklin, Marta Futema, Brown Sj, Francesco Cucca, Louise Gallagher, Matthias Geihs, Guangbiao Wang, Gabriela L. Surdulescu, Daniel H. Geschwind, Jun Wang, Heather Griffin, Yu Wang, Kirsten J. Ward, Shane A. McCarthy, Detelina Grozeva, Elanor Wheeler, Xiaosen Guo, Tamieka Whyte, Hywel Williams, Hugh M. D. Gurling, Xueqin Guo, Kathleen A. Williamson, Daniela Toniolo, Deborah J. Hart, Crispian Wilson, Audrey E. Hendricks, Colin M. Dayan, Kim Wong, Peter A. Holmans, ChangJiang Xu, Jian Yang

, Bryan N. Howie, Silvia Naitza, Fend Zhang, Pingbo Zhang, Bell Jt, Liren Huang, Tim J. P. Hubbard, John P. Walsh, Steve E. Humphries, Mullin Bh, Matthew E. Hurles, Louise V. Wain

, Pirro G. Hysi, David K. Jackson, Tim D. Spector, Yalda Jamshidi, Tian Jing, George Davey Smith, Chris Joyce, George Davey Smith, Jane Kaye, Thomas M. Keane, Shihab Ha, Richard M. Durbin, Julia M. Keogh, John P. Kemp, Karen L. Kennedy, Anja Kolb-Kokocinski, Genevieve Lachance, Cordelia Langford, Daniel J. Lawson, Irene Lee, Serena Sanna, Monkol Lek, Jieqin Liang, Hong Lin, Rui Li, Nicole Soranzo

, Yingrui Li, Ryan Liu, Jouko Lönnqvist, Margarida C. Lopes, Nicholas J. Timpson

, Valentina Lotchkova, P. W. Mcguffin, Daniel G. Macarthur, A. M. Mcintosh, Jonathan L. Marchini, A. G. Mckechanie, John Maslen, A. Mcquillin, Mangino Massimo, Jouko Lonnqvist, J. Brent Richards, Iain Mathieson, Gaëlle Marenne, Sarah J. Metrustry, Hannah M. Mitchison, Alireza Moayyeri, Peter McGuffin, James A. Morris, Andrew McIntosh

, Francesco M. Muntoni, Andrew G. McKechanie, Kate Northstone, Andrew McQuillin, Michael O'Donnovan, Alexandros Onoufriadis, Stephen P. O'Rahilly, Karim Oualkacha, Michael J. Owen, Aarno Palotie, Kalliope Panoutsopoulou, Victoria Parker, Jeremy R. Parr, Lavinia Paternoster, M. A. Quail, Tiina Paunio, Felicity Payne, Olli P. H. Pietilainen, Vincent Plagnol

, Lydia Quaye, Lucy F. Raymond, Karola Rehnström, J. Brent Richards, Susan M. Ring, Graham R. S. Ritchie, Michael A. Quai, Nicola Y. Roberts, David B. Savage, Peter J. Scambler, Stephen Schiffels, Miriam Schmidts

, Nadia A. Schoenmakers, Robert K. Semple, Eva Serra, Sally I. Sharp, So-Youn Shin, David H. Skuse, Kerrin S. Small, Lorraine Southam, David St Clair, Olivera Spasic-Boskovic, Jim W. Stalker, Barnes Mr, David St Clair, Elizabeth Stevens, Jianping Sun, Jaana M. Suvisaari, Ionna Tachmazidou, Beate St Pourcian, Martin D. Tobin, Beate St Pourcian, Ana A. Valdes, Margriet Van Kogelenberg, Parthiban Vijayarangakannan, Peter M. Visscher, Beilby Jp, Margriet Van Kogelenberg, Consortium Uk10k, U. K. K. Consortium, Consortium Uk0k, Scott Wilson

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Abstract

AbstractNormal 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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Whole-genome sequence-based analysis of thyroid function

Abstract