Whole-genome sequence-based analysis of thyroid function.
Whole-genome sequence-based analysis of thyroid function.
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DOI：
10.1038/ncomms6681
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发表时间：
2015-03-06
影响因子：
16.6
通讯作者：
Wilson, Scott G.
中科院分区：
文献类型：
--
作者：
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;Smith, George Davey;Durbin, Richard;Richards, J. Brent;Sanna, Serena;Soranzo, Nicole;Timpson, Nicholas J.;Wilson, Scott G.
正常的甲状腺功能对健康至关重要，但其遗传结构仍然知之甚少。在这里，对于可遗传的甲状腺性状促甲状腺激素（TSH）和游离甲状腺素（FT 4），我们分析了来自UK 10 K项目的全基因组序列数据（N= 2，287）。使用额外的全基因组序列和深度插补数据集，我们报告了与TSH和FT 4相关的常见变异（MAF≥1%）的荟萃分析结果（N= 16，335）。对于TSH，我们在SYN 2中发现了一个新的变异（MAF= 23.5%，P=6.15 × 10−9），在PDE 8B中发现了一个新的独立变异（MAF= 10.4%，P=5.94 × 10−14）。对于FT 4，我们报告了B4 GALT 6/SLC 25 A52附近的一个低频变异（MAF= 3.2%，P=1.27 × 10−9），标记了一个罕见的TTR变异（MAF= 0.4%，P=2.14 × 10−11）。所有常见变异可解释TSH和FT 4 ≥20%的变异。使用序列核关联测试分析罕见变异（MAF<1%）揭示了NRG 1中与FT 4的新关联。我们的研究结果表明，全基因组序列关联研究的覆盖率增加，确定了与甲状腺功能相关的新变异。 循环促甲状腺激素和游离甲状腺素水平反映甲状腺功能，然而，其遗传基础仍然知之甚少。Taylor等人利用UK 10 K项目中队列的全基因组序列数据来鉴定与这些性状相关的新变异。
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. Levels of circulating thyrotropin and free thyroxine reflect thyroid function, however, their genetic underpinnings remain poorly understood. Taylor et al. take advantage of whole-genome sequence data from cohorts within the UK10K project to identify novel variants associated with these traits.
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影响因子：
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通讯作者：
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