Genetic Pleiotropy between Nicotine Dependence and Respiratory Outcomes.
Genetic Pleiotropy between Nicotine Dependence and Respiratory Outcomes.
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尼古丁依赖与呼吸结果之间的遗传多效性
DOI：
10.1038/s41598-017-16964-4
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发表时间：
2017-12-04
影响因子：
4.6
通讯作者：
Hao K
中科院分区：
文献类型：
--
作者：
Zhang J;Peng S;Cheng H;Nomura Y;Di Narzo AF;Hao K
吸烟是呼吸系统疾病的主要原因。迄今为止，吸烟行为与肺功能/慢性阻塞性肺疾病（COPD）之间的遗传多效性尚未得到系统研究。我们利用吸烟行为、肺功能和COPD的大量数据集，解决了两个问题：（1）尼古丁依赖的遗传易感性是否影响COPD风险和肺功能;（2）遗传多效性遵循因果或独立模型。我们发现尼古丁依赖的遗传易感性与COPD风险相关，即使在调整吸烟行为后，也是如此，表明遗传多效性和独立模型。两个已知的尼古丁依赖位点（15q25.1和19q13.2）与吸烟调整的肺功能相关，15q25.1达到全基因组意义。在各种提示性p值阈值下，吸烟调整的肺功能性状与每日吸烟和既往吸烟共享关联信号，显著大于随机机会。经验数据显示尼古丁依赖与COPD或肺功能之间存在遗传多效性。多效性效应的基础相当复杂，归因于大量的遗传变异，并且许多变异通过独立的模型发挥作用，其中多效性变异直接影响肺功能，而不是通过影响受试者的吸烟行为来介导。
Smoking is a major cause of respiratory conditions. To date, the genetic pleiotropy between smoking behavior and lung function/chronic obstructive pulmonary disease (COPD) have not been systematically explored. We leverage large data sets of smoking behavior, lung function and COPD, and addressed two questions, (1) whether the genetic predisposition of nicotine dependence influence COPD risk and lung function; and (2) the genetic pleiotropy follow causal or independent model. We found the genetic predisposition of nicotine dependence was associated with COPD risk, even after adjusting for smoking behavior, indicating genetic pleiotropy and independent model. Two known nicotine dependent loci (15q25.1 and 19q13.2) were associated with smoking adjusted lung function, and 15q25.1 reached genome-wide significance. At various suggestive p-value thresholds, the smoking adjusted lung function traits share association signals with cigarettes per day and former smoking, substantially greater than random chance. Empirical data showed the genetic pleiotropy between nicotine dependence and COPD or lung function. The basis of pleiotropic effect is rather complex, attributable to a large number of genetic variants, and many variants functions through independent model, where the pleiotropic variants directly affect lung function, not mediated by influencing subjects’ smoking behavior.
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影响因子：
3.7
作者：
Ryan DM;Vincent TL;Salit J;Walters MS;Agosto-Perez F;Shaykhiev R;Strulovici-Barel Y;Downey RJ;Buro-Auriemma LJ;Staudt MR;Hackett NR;Mezey JG;Crystal RG
通讯作者：
Crystal RG
影响因子：
3.5
作者：
Cho, Michael H.;Castaldi, Peter J.;Silverman, Edwin K.
通讯作者：
Silverman, Edwin K.
影响因子：
30.8
作者：
Han B;Pouget JG;Slowikowski K;Stahl E;Lee CH;Diogo D;Hu X;Park YR;Kim E;Gregersen PK;Dahlqvist SR;Worthington J;Martin J;Eyre S;Klareskog L;Huizinga T;Chen WM;Onengut-Gumuscu S;Rich SS;Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium;Wray NR;Raychaudhuri S
通讯作者：
Raychaudhuri S
影响因子：
3.7
作者：
Harari O;Wang JC;Bucholz K;Edenberg HJ;Heath A;Martin NG;Pergadia ML;Montgomery G;Schrage A;Bierut LJ;Madden PF;Goate AM
通讯作者：
Goate AM
影响因子：
30.8
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
通讯作者：
International COPD Genetics Consortium