Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation.
Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation.
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DOI：
10.1038/ncomms9658
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发表时间：
2015-12-04
影响因子：
16.6
通讯作者：
Tobin MD
中科院分区：
文献类型：
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作者：
Soler Artigas M;Wain LV;Miller S;Kheirallah AK;Huffman JE;Ntalla I;Shrine N;Obeidat M;Trochet H;McArdle WL;Alves AC;Hui J;Zhao JH;Joshi PK;Teumer A;Albrecht E;Imboden M;Rawal R;Lopez LM;Marten J;Enroth S;Surakka I;Polasek O;Lyytikäinen LP;Granell R;Hysi PG;Flexeder C;Mahajan A;Beilby J;Bossé Y;Brandsma CA;Campbell H;Gieger C;Gläser S;González JR;Grallert H;Hammond CJ;Harris SE;Hartikainen AL;Heliövaara M;Henderson J;Hocking L;Horikoshi M;Hutri-Kähönen N;Ingelsson E;Johansson Å;Kemp JP;Kolcic I;Kumar A;Lind L;Melén E;Musk AW;Navarro P;Nickle DC;Padmanabhan S;Raitakari OT;Ried JS;Ripatti S;Schulz H;Scott RA;Sin DD;Starr JM;UK BiLEVE;Viñuela A;Völzke H;Wild SH;Wright AF;Zemunik T;Jarvis DL;Spector TD;Evans DM;Lehtimäki T;Vitart V;Kähönen M;Gyllensten U;Rudan I;Deary IJ;Karrasch S;Probst-Hensch NM;Heinrich J;Stubbe B;Wilson JF;Wareham NJ;James AL;Morris AP;Jarvelin MR;Hayward C;Sayers I;Strachan DP;Hall IP;Tobin MD
肺功能指标用于慢性阻塞性肺疾病的诊断。在38199名欧洲血统的个体中，我们研究了1秒用力呼气量（FEV1）、用力肺活量（FVC）以及FEV1/FVC与千人基因组计划（第一阶段）填补基因型的全基因组关联，并在54550名欧洲人中对主要关联进行了后续研究。我们在ENSA、RNU5F - 1、KCNS3、AK097794、ASTN2、LHX3、CCDC91、TBX3、TRIP11、RIN3、TEKT5、LTBP4、MN1和AP1S2内部或附近确定了14个新的基因位点（P<5×10⁻⁸），以及在已知基因位点NPNT和GPR126的两个新信号，为这些性状以及它们发生改变的肺部疾病的遗传决定因素提供了新的认识基础。
遗传和环境因素影响肺功能，这在肺部疾病的诊断中很重要。在这里，作者利用对千人基因组计划参考面板的基因型填补来确定与肺功能相关的新的低频变异。
Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10−8) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered. Genetic and environmental factors impact on lung function, important in the diagnosis of pulmonary diseases. Here the authors use imputation of genotypes to the 1000 Genomes Project reference panel to identify novel, low frequency variants associated with lung function.