Journal
NATURE COMMUNICATIONS
Volume 6, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms6681
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Funding
- Wellcome Trust [WT091310]
- Biotechnology and Biological Sciences Research Council [BB/I025751/1, BB/I025263/1] Funding Source: researchfish
- Medical Research Council [MC_UU_12013/3, MC_UU_12013/8, MC_UU_12013/2, MC_U106179472, MR/K006215/1, MC_UU_12015/2, MC_UU_12012/5/B, MC_PC_15018, MR/L010305/1] Funding Source: researchfish
- BBSRC [BB/I025263/1, BB/I025751/1] Funding Source: UKRI
- MRC [MC_UU_12013/2, MR/K006215/1, MC_UU_12013/3, MC_UU_12015/2, MC_UU_12013/8, MC_U106179472] Funding Source: UKRI
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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 x 10(-9)) and a new independent variant in PDE8B (MAF = 10.4%, P = 5.94 x 10(-14)). For FT4, we report a low-frequency variant near B4GALT6/ SLC25A52 (MAF = 3.2%, P = 1.27 x 10(-9)) tagging a rare TTR variant (MAF = 0.4%, P = 2.14 x 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.
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