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Whole-genome sequence-based analysis of thyroid function

Lookup NU author(s): Dr Mattia Calissano, Professor Jeremy Parr

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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.


Publication metadata

Author(s): 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 H-F, 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, Lonnqvist 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, Rehnstrom 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 S-Y, 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

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2015

Volume: 6

Online publication date: 06/03/2015

Acceptance date: 27/10/2014

ISSN (electronic): 2041-1723

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/ncomms6681

DOI: 10.1038/ncomms6681


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