Back to Search Start Over

Whole-genome sequence-based analysis of thyroid function

Authors :
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.
Charoen, Pimphen
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
Davey Smith, George
Durbin, Richard
Brent Richards, J.
Sanna, Serena
Soranzo, Nicole
Timpson, Nicholas J.
Wilson, Scott G.
Turki, Saeed Al
Anderson, Carl
Anney, Richard
Antony, Dinu
Artigas, Maria Soler
Ayub, Muhammad
Balasubramaniam, Senduran
Barrett, Jeffrey C.
Barroso, Inês
Beales, Phil
Bentham, Jamie
Bhattacharya, Shoumo
Birney, Ewan
Blackwood, Douglas
Bobrow, Martin
Bochukova, Elena
Bolton, Patrick
Bounds, Rebecca
Boustred, Chris
Breen, Gerome
Calissano, Mattia
Carss, Keren
Chatterjee, Krishna
Chen, Lu
Ciampi, Antonio
Cirak, Sebhattin
Clapham, Peter
Clement, Gail
Coates, Guy
Collier, David
Cosgrove, Catherine
Cox, Tony
Craddock, Nick
Crooks, Lucy
Curran, Sarah
Curtis, David
Daly, Allan
Day-Williams, Aaron
Day, Ian N.M.
Down, Thomas
Du, Yuanping
Dunham, Ian
Edkins, Sarah
Ellis, Peter
Evans, David
Faroogi, Sadaf
Fatemifar, Ghazaleh
Fitzpatrick, David R.
Flicek, Paul
Flyod, James
Foley, A. Reghan
Franklin, Christopher S.
Futema, Marta
Gallagher, Louise
Geihs, Matthias
Geschwind, Daniel
Griffin, Heather
Grozeva, Detelina
Guo, Xueqin
Guo, Xiaosen
Gurling, Hugh
Hart, Deborah
Hendricks, Audrey
Holmans, Peter
Howie, Bryan
Huang, Liren
Hubbard, Tim
Humphries, Steve E.
Hurles, Matthew E.
Hysi, Pirro
Jackson, David K.
Jamshidi, Yalda
Jing, Tian
Joyce, Chris
Kaye, Jane
Keane, Thomas
Keogh, Julia
Kemp, John
Kennedy, Karen
Kolb-Kokocinski, Anja
Lachance, Genevieve
Langford, Cordelia
Lawson, Daniel
Lee, Irene
Lek, Monkol
Liang, Jieqin
Lin, Hong
Li, Rui
Li, Yingrui
Liu, Ryan
Lönnqvist, Jouko
Lopes, Margarida
Lotchkova, Valentina
MacArthur, Daniel
Marchini, Jonathan
Maslen, John
Massimo, Mangino
Mathieson, Iain
Marenne, Gaëlle
McGuffin, Peter
McIntosh, Andrew
McKechanie, Andrew G.
McQuillin, Andrew
Metrustry, Sarah
Mitchison, Hannah
Moayyeri, Alireza
Morris, James
Muntoni, Francesco
Northstone, Kate
O'Donnovan, Michael
Onoufriadis, Alexandros
O'Rahilly, Stephen
Oualkacha, Karim
Owen, Michael J.
Palotie, Aarno
Panoutsopoulou, Kalliope
Parker, Victoria
Parr, Jeremy R.
Paternoster, Lavinia
Paunio, Tiina
Payne, Felicity
Pietilainen, Olli
Plagnol, Vincent
Quaye, Lydia
Quai, Michael A.
Raymond, Lucy
Rehnström, Karola
Richards, Brent
Ring, Susan
Ritchie, Graham R.S.
Roberts, Nicola
Savage, David B.
Scambler, Peter
Schiffels, Stephen
Schmidts, Miriam
Schoenmakers, Nadia
Semple, Robert K.
Serra, Eva
Sharp, Sally I.
Shin, So-Youn
Skuse, David
Small, Kerrin
Southam, Lorraine
Spasic-Boskovic, Olivera
Clair, David St
Stalker, Jim
Stevens, Elizabeth
Pourcian, Beate St
Sun, Jianping
Suvisaari, Jaana
Tachmazidou, Ionna
Tobin, Martin D.
Valdes, Ana
Kogelenberg, Margriet Van
Vijayarangakannan, Parthiban
Visscher, Peter M.
Wain, Louise V.
Walters, James T.R.
Wang, Guangbiao
Wang, Jun
Wang, Yu
Ward, Kirsten
Wheeler, Elanor
Whyte, Tamieka
Williams, Hywel
Williamson, Kathleen A.
Wilson, Crispian
Wong, Kim
Xu, ChangJiang
Yang, Jian
Zhang, Fend
Zhang, Pingbo
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.
Charoen, Pimphen
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
Davey Smith, George
Durbin, Richard
Brent Richards, J.
Sanna, Serena
Soranzo, Nicole
Timpson, Nicholas J.
Wilson, Scott G.
Turki, Saeed Al
Anderson, Carl
Anney, Richard
Antony, Dinu
Artigas, Maria Soler
Ayub, Muhammad
Balasubramaniam, Senduran
Barrett, Jeffrey C.
Barroso, Inês
Beales, Phil
Bentham, Jamie
Bhattacharya, Shoumo
Birney, Ewan
Blackwood, Douglas
Bobrow, Martin
Bochukova, Elena
Bolton, Patrick
Bounds, Rebecca
Boustred, Chris
Breen, Gerome
Calissano, Mattia
Carss, Keren
Chatterjee, Krishna
Chen, Lu
Ciampi, Antonio
Cirak, Sebhattin
Clapham, Peter
Clement, Gail
Coates, Guy
Collier, David
Cosgrove, Catherine
Cox, Tony
Craddock, Nick
Crooks, Lucy
Curran, Sarah
Curtis, David
Daly, Allan
Day-Williams, Aaron
Day, Ian N.M.
Down, Thomas
Du, Yuanping
Dunham, Ian
Edkins, Sarah
Ellis, Peter
Evans, David
Faroogi, Sadaf
Fatemifar, Ghazaleh
Fitzpatrick, David R.
Flicek, Paul
Flyod, James
Foley, A. Reghan
Franklin, Christopher S.
Futema, Marta
Gallagher, Louise
Geihs, Matthias
Geschwind, Daniel
Griffin, Heather
Grozeva, Detelina
Guo, Xueqin
Guo, Xiaosen
Gurling, Hugh
Hart, Deborah
Hendricks, Audrey
Holmans, Peter
Howie, Bryan
Huang, Liren
Hubbard, Tim
Humphries, Steve E.
Hurles, Matthew E.
Hysi, Pirro
Jackson, David K.
Jamshidi, Yalda
Jing, Tian
Joyce, Chris
Kaye, Jane
Keane, Thomas
Keogh, Julia
Kemp, John
Kennedy, Karen
Kolb-Kokocinski, Anja
Lachance, Genevieve
Langford, Cordelia
Lawson, Daniel
Lee, Irene
Lek, Monkol
Liang, Jieqin
Lin, Hong
Li, Rui
Li, Yingrui
Liu, Ryan
Lönnqvist, Jouko
Lopes, Margarida
Lotchkova, Valentina
MacArthur, Daniel
Marchini, Jonathan
Maslen, John
Massimo, Mangino
Mathieson, Iain
Marenne, Gaëlle
McGuffin, Peter
McIntosh, Andrew
McKechanie, Andrew G.
McQuillin, Andrew
Metrustry, Sarah
Mitchison, Hannah
Moayyeri, Alireza
Morris, James
Muntoni, Francesco
Northstone, Kate
O'Donnovan, Michael
Onoufriadis, Alexandros
O'Rahilly, Stephen
Oualkacha, Karim
Owen, Michael J.
Palotie, Aarno
Panoutsopoulou, Kalliope
Parker, Victoria
Parr, Jeremy R.
Paternoster, Lavinia
Paunio, Tiina
Payne, Felicity
Pietilainen, Olli
Plagnol, Vincent
Quaye, Lydia
Quai, Michael A.
Raymond, Lucy
Rehnström, Karola
Richards, Brent
Ring, Susan
Ritchie, Graham R.S.
Roberts, Nicola
Savage, David B.
Scambler, Peter
Schiffels, Stephen
Schmidts, Miriam
Schoenmakers, Nadia
Semple, Robert K.
Serra, Eva
Sharp, Sally I.
Shin, So-Youn
Skuse, David
Small, Kerrin
Southam, Lorraine
Spasic-Boskovic, Olivera
Clair, David St
Stalker, Jim
Stevens, Elizabeth
Pourcian, Beate St
Sun, Jianping
Suvisaari, Jaana
Tachmazidou, Ionna
Tobin, Martin D.
Valdes, Ana
Kogelenberg, Margriet Van
Vijayarangakannan, Parthiban
Visscher, Peter M.
Wain, Louise V.
Walters, James T.R.
Wang, Guangbiao
Wang, Jun
Wang, Yu
Ward, Kirsten
Wheeler, Elanor
Whyte, Tamieka
Williams, Hywel
Williamson, Kathleen A.
Wilson, Crispian
Wong, Kim
Xu, ChangJiang
Yang, Jian
Zhang, Fend
Zhang, Pingbo
Publication Year :
2015

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.

Details

Database :
OAIster
Notes :
application/pdf, 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.; Charoen, Pimphen; 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; Davey Smith, George; Durbin, Richard; Brent Richards, J.; Sanna, Serena; Soranzo, Nicole; Timpson, Nicholas J.; Wilson, Scott G.; Turki, Saeed Al; Anderson, Carl; Anney, Richard; Antony, Dinu; Artigas, Maria Soler; Ayub, Muhammad; Balasubramaniam, Senduran; Barrett, Jeffrey C.; Barroso, Inês; Beales, Phil; Bentham, Jamie; Bhattacharya, Shoumo; Birney, Ewan; Blackwood, Douglas; Bobrow, Martin; Bochukova, Elena; Bolton, Patrick; Bounds, Rebecca; Boustred, Chris; Breen, Gerome; Calissano, Mattia; Carss, Keren; Chatterjee, Krishna; Chen, Lu; Ciampi, Antonio; Cirak, Sebhattin; Clapham, Peter; Clement, Gail; Coates, Guy; Collier, David; Cosgrove, Catherine; Cox, Tony; Craddock, Nick; Crooks, Lucy; Curran, Sarah; Curtis, David; Daly, Allan; Day-Williams, Aaron; Day, Ian N.M.; Down, Thomas; Du, Yuanping; Dunham, Ian; Edkins, Sarah; Ellis, Peter; Evans, David; Faroogi, Sadaf; Fatemifar, Ghazaleh; Fitzpatrick, David R.; Flicek, Paul; Flyod, James; Foley, A. Reghan; Franklin, Christopher S.; Futema, Marta; Gallagher, Louise; Geihs, Matthias; Geschwind, Daniel; Griffin, Heather; Grozeva, Detelina; Guo, Xueqin; Guo, Xiaosen; Gurling, Hugh; Hart, Deborah; Hendricks, Audrey; Holmans, Peter; Howie, Bryan; Huang, Liren; Hubbard, Tim; Humphries, Steve E., English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1142174962
Document Type :
Electronic Resource