Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis.
Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis.
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DOI：
10.1038/ng.3752
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发表时间：
2017-03
期刊：
影响因子：
30.8
通讯作者：
International COPD Genetics Consortium
中科院分区：
文献类型：
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作者：
Hobbs BD;de Jong K;Lamontagne M;Bossé Y;Shrine N;Artigas MS;Wain LV;Hall IP;Jackson VE;Wyss AB;London SJ;North KE;Franceschini N;Strachan DP;Beaty TH;Hokanson JE;Crapo JD;Castaldi PJ;Chase RP;Bartz TM;Heckbert SR;Psaty BM;Gharib SA;Zanen P;Lammers JW;Oudkerk M;Groen HJ;Locantore N;Tal-Singer R;Rennard SI;Vestbo J;Timens W;Paré PD;Latourelle JC;Dupuis J;O'Connor GT;Wilk JB;Kim WJ;Lee MK;Oh YM;Vonk JM;de Koning HJ;Leng S;Belinsky SA;Tesfaigzi Y;Manichaikul A;Wang XQ;Rich SS;Barr RG;Sparrow D;Litonjua AA;Bakke P;Gulsvik A;Lahousse L;Brusselle GG;Stricker BH;Uitterlinden AG;Ampleford EJ;Bleecker ER;Woodruff PG;Meyers DA;Qiao D;Lomas DA;Yim JJ;Kim DK;Hawrylkiewicz I;Sliwinski P;Hardin M;Fingerlin TE;Schwartz DA;Postma DS;MacNee W;Tobin MD;Silverman EK;Boezen HM;Cho MH;COPDGene Investigators;ECLIPSE Investigators;LifeLines Investigators;SPIROMICS Research Group;International COPD Genetics Network Investigators;UK BiLEVE Investigators;International COPD Genetics Consortium
慢性阻塞性肺疾病(COPD)是世界范围内导致死亡的主要原因。我们在15,256名病例和47,936名对照中进行了基因关联研究，在9,498名病例和9,748名对照中复制了精选TOP结果(P<；5×10−6)。在联合荟萃分析中，我们确定了22个在全基因组意义上相关的基因座，其中包括13个与COPD有关的新基因。在普通人群样本中，这13个基因座中有9个与肺功能有关，而4个(EEFSEC、DSP、MTCL1和SFTPD)是新的。我们注意到了两个与肺纤维化有共同作用的基因座(FAM13A和DSP)，但这两个基因座具有相反的COPD风险等位基因。我们没有一个基因座与哮喘的全基因组关联重叠，尽管有一个基因座与哮喘和肥胖症的联合易感性有关。我们还确定了COPD和哮喘之间的遗传相关性。我们的发现突出了与COPD相关的新的基因座，证明了与肺功能相关的特定基因座对COPD的重要性，并确定了COPD和其他呼吸系统疾病之间潜在的遗传重叠区域。
Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P< 5 × 10−6) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci associated at genome-wide significance, including 13 new associations with COPD. Nine of these 13 loci have been associated with lung function in general population samples,,,,,, while 4 (EEFSEC,DSP,MTCL1, andSFTPD) are new. We noted two loci shared with pulmonary fibrosis,(FAM13AandDSP) but that had opposite risk alleles for COPD. None of our loci overlapped with genome-wide associations for asthma, although one locus has been implicated in joint susceptibility to asthma and obesity. We also identified genetic correlation between COPD and asthma. Our findings highlight new loci associated with COPD, demonstrate the importance of specific loci associated with lung function to COPD, and identify potential regions of genetic overlap between COPD and other respiratory diseases.