Taylor, Peter N. ![]() ![]() ![]() ![]() ![]() ![]() |
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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.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Research Institutes & Centres > Neuroscience and Mental Health Research Institute (NMHII) Schools > Medicine Research Institutes & Centres > MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) |
Subjects: | R Medicine > R Medicine (General) |
Additional Information: | Nick Craddock, Peter Holmans, Michael O'Donovan, Michael Owen and James Walters are collaborators on this article. The UK10K Consortium |
Publisher: | Nature Research |
ISSN: | 2041-1723 |
Date of First Compliant Deposit: | 13 September 2017 |
Date of Acceptance: | 27 October 2014 |
Last Modified: | 07 May 2023 19:36 |
URI: | https://orca.cardiff.ac.uk/id/eprint/85638 |
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