Whole-genome sequence-based analysis of thyroid function

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...

Full description

Saved in:
Bibliographic Details
Published in:Nature communications 2015-03, Vol.6 (1), p.5681-5681, Article 5681
Main 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.
Format: Article
Language:English
Subjects:
3',5'-Cyclic-AMP Phosphodiesterases - genetics
3',5'-Cyclic-AMP Phosphodiesterases - metabolism
38
631/1647/2217/2220
631/208/726/649/2219
631/45/776/1180
692/308/2779/109
Cohort Studies
DNA Methylation - genetics
Genetic Association Studies
Genomics - methods
Humanities and Social Sciences
Humans
multidisciplinary
Science
Science (multidisciplinary)
Synapsins - genetics
Synapsins - metabolism
Thyroid Gland - metabolism
Thyroid Gland - physiology
Thyrotropin - genetics
Thyrotropin - metabolism
Thyroxine - genetics
Thyroxine - metabolism
United Kingdom
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms6681