Whole-genome sequence-based analysis of thyroid function

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. Quail; 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; Chang Jiang Xu; Jian Yang; Fend Zhang; Pingbo Zhang

doi:10.1038/ncomms6681

Whole-genome sequence-based analysis of thyroid function

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 GrundbergAndrew 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. Quail, 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, Chang Jiang Xu, Jian Yang, Fend Zhang, Pingbo Zhang

^*Corresponding author af dette arbejde

Genomforskning og Molekylær Biomedicin

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

81 Citationer (Scopus)

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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.

Originalsprog	Engelsk
Artikelnummer	5681
Tidsskrift	Nature Communications
Vol/bind	6
Antal sider	11
ISSN	2041-1723
DOI	https://doi.org/10.1038/ncomms6681
Status	Udgivet - 2015

Adgang til dokumentet

10.1038/ncomms6681

Whole-genome sequence-based analysis of thyroid functionForlagets udgivne version, 1,15 MB

Citationsformater

Taylor, P. N., Porcu, E., Chew, S., Campbell, P. J., Traglia, M., Brown, S. J., Mullin, B. H., Shihab, H. A., Min, J., Walter, K., Memari, Y., Huang, J., Barnes, M. R., Beilby, J. P., Charoen, P., Danecek, P., Dudbridge, F., Forgetta, V., Greenwood, C., ... Zhang, P. (2015). Whole-genome sequence-based analysis of thyroid function. Nature Communications, 6, Artikel 5681. https://doi.org/10.1038/ncomms6681

Taylor, PN, Porcu, E, Chew, S, Campbell, PJ, Traglia, M, Brown, SJ, Mullin, BH, Shihab, HA, Min, J, Walter, K, Memari, Y, Huang, J, Barnes, MR, Beilby, JP, Charoen, P, Danecek, P, Dudbridge, F, Forgetta, V, Greenwood, C, Grundberg, E, Johnson, AD, Hui, J, Lim, EM, McCarthy, S, Muddyman, D, Panicker, V, Perry, JRB, Bell, JT, Yuan, W, Relton, C, Gaunt, T, Schlessinger, D, Abecasis, G, Cucca, F, Surdulescu, GL, Woltersdorf, W, Zeggini, E, Zheng, HF, Toniolo, D, Dayan, CM, Naitza, S, Walsh, JP, Spector, T, Smith, GD, Durbin, R, Richards, JB, Sanna, S, Soranzo, N, Timpson, NJ, Wilson, SG, Turki, SA, Anderson, C, Anney, R, Antony, D, Artigas, MS, Ayub, M, Balasubramaniam, S, Barrett, JC, Barroso, I, Beales, P, Bentham, J, Bhattacharya, S, Birney, E, Blackwood, D, Bobrow, M, Bochukova, E, Bolton, P, Bounds, R, Boustred, C, Breen, G, Calissano, M, Carss, K, Chatterjee, K, Chen, L, Ciampi, A, Cirak, S, Clapham, P, Clement, G, Coates, G, Collier, D, Cosgrove, C, Cox, T, Craddock, N, Crooks, L, Curran, S, Curtis, D, Daly, A, Day-Williams, A, Day, INM, Down, T, Du, Y, Dunham, I, Edkins, S, Ellis, P, Evans, D, Faroogi, S, Fatemifar, G, Fitzpatrick, DR, Flicek, P, Flyod, J, Foley, AR, Franklin, CS, Futema, M, Gallagher, L, Geihs, M, Geschwind, D, Griffin, H, Grozeva, D, Guo, X, Guo, X, Gurling, H, Hart, D, Hendricks, A, Holmans, P, Howie, B, Huang, L, Hubbard, T, Humphries, SE, Hurles, ME, Hysi, P, Jackson, DK, Jamshidi, Y, Jing, T, Joyce, C, Kaye, J, Keane, T, Keogh, J, Kemp, J, Kennedy, K, Kolb-Kokocinski, A, Lachance, G, Langford, C, Lawson, D, Lee, I, Lek, M, Liang, J, Lin, H, Li, R, Li, Y, Liu, R, Lönnqvist, J, Lopes, M, Lotchkova, V, MacArthur, D, Marchini, J, Maslen, J, Massimo, M, Mathieson, I, Marenne, G, McGuffin, P, McIntosh, A, McKechanie, AG, McQuillin, A, Metrustry, S, Mitchison, H, Moayyeri, A, Morris, J, Muntoni, F, Northstone, K, O'Donnovan, M, Onoufriadis, A, O'Rahilly, S, Oualkacha, K, Owen, MJ, Palotie, A, Panoutsopoulou, K, Parker, V, Parr, JR, Paternoster, L, Paunio, T, Payne, F, Pietilainen, O, Plagnol, V, Quaye, L, Quail, MA, Raymond, L, Rehnström, K, Richards, B, Ring, S, Ritchie, GRS, Roberts, N, Savage, DB, Scambler, P, Schiffels, S, Schmidts, M, Schoenmakers, N, Semple, RK, Serra, E, Sharp, SI, Shin, SY, Skuse, D, Small, K, Southam, L, Spasic-Boskovic, O, Clair, DS, Stalker, J, Stevens, E, Pourcian, BS, Sun, J, Suvisaari, J, Tachmazidou, I, Tobin, MD, Valdes, A, Van Kogelenberg, M, Vijayarangakannan, P, Visscher, PM, Wain, LV, Walters, JTR, Wang, G, Wang, J, Wang, Y, Ward, K, Wheeler, E, Whyte, T, Williams, H, Williamson, KA, Wilson, C, Wong, K, Xu, CJ, Yang, J, Zhang, F & Zhang, P 2015, 'Whole-genome sequence-based analysis of thyroid function', Nature Communications, bind 6, 5681. https://doi.org/10.1038/ncomms6681

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title = "Whole-genome sequence-based analysis of thyroid function",

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.",

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

year = "2015",

doi = "10.1038/ncomms6681",

language = "English",

volume = "6",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "nature publishing group",

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TY - JOUR

T1 - Whole-genome sequence-based analysis of thyroid function

AU - Taylor, Peter N.

AU - Porcu, Eleonora

AU - Chew, Shelby

AU - Campbell, Purdey J.

AU - Traglia, Michela

AU - Brown, Suzanne J.

AU - Mullin, Benjamin H.

AU - Shihab, Hashem A.

AU - Min, Josine

AU - Walter, Klaudia

AU - Memari, Yasin

AU - Huang, Jie

AU - Barnes, Michael R.

AU - Beilby, John P.

AU - Charoen, Pimphen

AU - Danecek, Petr

AU - Dudbridge, Frank

AU - Forgetta, Vincenzo

AU - Greenwood, Celia

AU - Grundberg, Elin

AU - Johnson, Andrew D.

AU - Hui, Jennie

AU - Lim, Ee M.

AU - McCarthy, Shane

AU - Muddyman, Dawn

AU - Panicker, Vijay

AU - Perry, John R B

AU - Bell, Jordana T.

AU - Yuan, Wei

AU - Relton, Caroline

AU - Gaunt, Tom

AU - Schlessinger, David

AU - Abecasis, Goncalo

AU - Cucca, Francesco

AU - Surdulescu, Gabriela L.

AU - Woltersdorf, Wolfram

AU - Zeggini, Eleftheria

AU - Zheng, Hou Feng

AU - Toniolo, Daniela

AU - Dayan, Colin M.

AU - Naitza, Silvia

AU - Walsh, John P.

AU - Spector, Tim

AU - Smith, George Davey

AU - Durbin, Richard

AU - Richards, J. Brent

AU - Sanna, Serena

AU - Soranzo, Nicole

AU - Timpson, Nicholas J.

AU - Wilson, Scott G.

AU - Turki, Saeed Al

AU - Anderson, Carl

AU - Anney, Richard

AU - Antony, Dinu

AU - Artigas, Maria Soler

AU - Ayub, Muhammad

AU - Balasubramaniam, Senduran

AU - Barrett, Jeffrey C.

AU - Barroso, Inês

AU - Beales, Phil

AU - Bentham, Jamie

AU - Bhattacharya, Shoumo

AU - Birney, Ewan

AU - Blackwood, Douglas

AU - Bobrow, Martin

AU - Bochukova, Elena

AU - Bolton, Patrick

AU - Bounds, Rebecca

AU - Boustred, Chris

AU - Breen, Gerome

AU - Calissano, Mattia

AU - Carss, Keren

AU - Chatterjee, Krishna

AU - Chen, Lu

AU - Ciampi, Antonio

AU - Cirak, Sebhattin

AU - Clapham, Peter

AU - Clement, Gail

AU - Coates, Guy

AU - Collier, David

AU - Cosgrove, Catherine

AU - Cox, Tony

AU - Craddock, Nick

AU - Crooks, Lucy

AU - Curran, Sarah

AU - Curtis, David

AU - Daly, Allan

AU - Day-Williams, Aaron

AU - Day, Ian N M

AU - Down, Thomas

AU - Du, Yuanping

AU - Dunham, Ian

AU - Edkins, Sarah

AU - Ellis, Peter

AU - Evans, David

AU - Faroogi, Sadaf

AU - Fatemifar, Ghazaleh

AU - Fitzpatrick, David R.

AU - Flicek, Paul

AU - Flyod, James

AU - Foley, A. Reghan

AU - Franklin, Christopher S.

AU - Futema, Marta

AU - Gallagher, Louise

AU - Geihs, Matthias

AU - Geschwind, Daniel

AU - Griffin, Heather

AU - Grozeva, Detelina

AU - Guo, Xueqin

AU - Guo, Xiaosen

AU - Gurling, Hugh

AU - Hart, Deborah

AU - Hendricks, Audrey

AU - Holmans, Peter

AU - Howie, Bryan

AU - Huang, Liren

AU - Hubbard, Tim

AU - Humphries, Steve E.

AU - Hurles, Matthew E.

AU - Hysi, Pirro

AU - Jackson, David K.

AU - Jamshidi, Yalda

AU - Jing, Tian

AU - Joyce, Chris

AU - Kaye, Jane

AU - Keane, Thomas

AU - Keogh, Julia

AU - Kemp, John

AU - Kennedy, Karen

AU - Kolb-Kokocinski, Anja

AU - Lachance, Genevieve

AU - Langford, Cordelia

AU - Lawson, Daniel

AU - Lee, Irene

AU - Lek, Monkol

AU - Liang, Jieqin

AU - Lin, Hong

AU - Li, Rui

AU - Li, Yingrui

AU - Liu, Ryan

AU - Lönnqvist, Jouko

AU - Lopes, Margarida

AU - Lotchkova, Valentina

AU - MacArthur, Daniel

AU - Marchini, Jonathan

AU - Maslen, John

AU - Massimo, Mangino

AU - Mathieson, Iain

AU - Marenne, Gaëlle

AU - McGuffin, Peter

AU - McIntosh, Andrew

AU - McKechanie, Andrew G.

AU - McQuillin, Andrew

AU - Metrustry, Sarah

AU - Mitchison, Hannah

AU - Moayyeri, Alireza

AU - Morris, James

AU - Muntoni, Francesco

AU - Northstone, Kate

AU - O'Donnovan, Michael

AU - Onoufriadis, Alexandros

AU - O'Rahilly, Stephen

AU - Oualkacha, Karim

AU - Owen, Michael J.

AU - Palotie, Aarno

AU - Panoutsopoulou, Kalliope

AU - Parker, Victoria

AU - Parr, Jeremy R.

AU - Paternoster, Lavinia

AU - Paunio, Tiina

AU - Payne, Felicity

AU - Pietilainen, Olli

AU - Plagnol, Vincent

AU - Quaye, Lydia

AU - Quail, Michael A.

AU - Raymond, Lucy

AU - Rehnström, Karola

AU - Richards, Brent

AU - Ring, Susan

AU - Ritchie, Graham R S

AU - Roberts, Nicola

AU - Savage, David B.

AU - Scambler, Peter

AU - Schiffels, Stephen

AU - Schmidts, Miriam

AU - Schoenmakers, Nadia

AU - Semple, Robert K.

AU - Serra, Eva

AU - Sharp, Sally I.

AU - Shin, So Youn

AU - Skuse, David

AU - Small, Kerrin

AU - Southam, Lorraine

AU - Spasic-Boskovic, Olivera

AU - Clair, David St

AU - Stalker, Jim

AU - Stevens, Elizabeth

AU - Pourcian, Beate St

AU - Sun, Jianping

AU - Suvisaari, Jaana

AU - Tachmazidou, Ionna

AU - Tobin, Martin D.

AU - Valdes, Ana

AU - Van Kogelenberg, Margriet

AU - Vijayarangakannan, Parthiban

AU - Visscher, Peter M.

AU - Wain, Louise V.

AU - Walters, James T R

AU - Wang, Guangbiao

AU - Wang, Jun

AU - Wang, Yu

AU - Ward, Kirsten

AU - Wheeler, Elanor

AU - Whyte, Tamieka

AU - Williams, Hywel

AU - Williamson, Kathleen A.

AU - Wilson, Crispian

AU - Wong, Kim

AU - Xu, Chang Jiang

AU - Yang, Jian

AU - Zhang, Fend

AU - Zhang, Pingbo

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

U2 - 10.1038/ncomms6681

DO - 10.1038/ncomms6681

M3 - Journal article

C2 - 25743335

AN - SCOPUS:84924347503

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 5681

ER -