Evidence for large-scale gene-by-smoking interaction effects on pulmonary function.
Evidence for large-scale gene-by-smoking interaction effects on pulmonary function.
复制标题
DOI：
10.1093/ije/dyw318
复制
发表时间：
2017-06-01
影响因子：
7.7
通讯作者：
Kraft P
中科院分区：
文献类型：
--
作者：
Aschard H;Tobin MD;Hancock DB;Skurnik D;Sood A;James A;Vernon Smith A;Manichaikul AW;Campbell A;Prins BP;Hayward C;Loth DW;Porteous DJ;Strachan DP;Zeggini E;O'Connor GT;Brusselle GG;Boezen HM;Schulz H;Deary IJ;Hall IP;Rudan I;Kaprio J;Wilson JF;Wilk JB;Huffman JE;Hua Zhao J;de Jong K;Lyytikäinen LP;Wain LV;Jarvelin MR;Kähönen M;Fornage M;Polasek O;Cassano PA;Barr RG;Rawal R;Harris SE;Gharib SA;Enroth S;Heckbert SR;Lehtimäki T;Gyllensten U;Understanding Society Scientific Group;Jackson VE;Gudnason V;Tang W;Dupuis J;Soler Artigas M;Joshi AD;London SJ;Kraft P
背景：吸烟是导致肺功能降低的最强烈的环境危险因素。各种肺部性状的遗传成分也已被证明，至少有26个基因座与FEV1(1秒用力呼气量)或FEV1/FVC(FEV1/用力肺活量)可重复相关。虽然吸烟和遗传位点的主要效应已经确定，但潜在的基因对吸烟的交互作用的问题仍然没有得到回答。本研究的目的是使用遗传风险评分方法评估这26个基因座对肺功能的影响是否受吸烟的影响。方法：我们评估了吸烟暴露与26个单核苷酸多态(SNPs)与FEV1或FEV1/FVC之间的交互作用。这些SNPs来自心脏和衰老基因组流行病学队列研究(CHARD)和SproMeta联合体中的50 047名欧洲血统的参与者。结果：我们确定了未加权的26SNP遗传风险评分与吸烟(曾经/从不吸烟)对FEV1/FVC比率的交互作用(βINT = -0.036，95%可信区间，-0.040至-0.032，P = 0.00057)。在解释这种相互作用时，我们发现，在吸烟者中，低于用于诊断慢性阻塞性肺疾病的FEV1/FVC阈值的遗传风险高于从不吸烟者。对两个独立数据集的重复分析，虽然在统计学上没有显著意义，但在交互作用方面显示出类似的趋势。结论：这项研究强调了在研究个体SNPs时使用遗传风险评分来识别遗漏的交互作用的好处，并首次表明，FEV1/FVC低的遗传风险最高的人可能更容易受到吸烟的有害影响。
Background: Smoking is the strongest environmental risk factor for reduced pulmonary function. The genetic component of various pulmonary traits has also been demonstrated, and at least 26 loci have been reproducibly associated with either FEV1 (forced expiratory volume in 1 second) or FEV1/FVC (FEV1/forced vital capacity). Although the main effects of smoking and genetic loci are well established, the question of potential gene-by-smoking interaction effect remains unanswered. The aim of the present study was to assess, using a genetic risk score approach, whether the effect of these 26 loci on pulmonary function is influenced by smoking. Methods: We evaluated the interaction between smoking exposure, considered as either ever vs never or pack-years, and a 26-single nucleotide polymorphisms (SNPs) genetic risk score in relation to FEV1 or FEV1/FVC in 50 047 participants of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) and SpiroMeta consortia. Results: We identified an interaction (βint = –0.036, 95% confidence interval, –0.040 to –0.032, P = 0.00057) between an unweighted 26 SNP genetic risk score and smoking status (ever/never) on the FEV1/FVC ratio. In interpreting this interaction, we showed that the genetic risk of falling below the FEV1/FVC threshold used to diagnose chronic obstructive pulmonary disease is higher among ever smokers than among never smokers. A replication analysis in two independent datasets, although not statistically significant, showed a similar trend in the interaction effect. Conclusions: This study highlights the benefit of using genetic risk scores for identifying interactions missed when studying individual SNPs and shows, for the first time, that persons with the highest genetic risk for low FEV1/FVC may be more susceptible to the deleterious effects of smoking.
登录
查看更多内容
影响因子：
5.4
作者：
Aschard, Hugues;Zaitlen, Noah;Kraft, Peter
通讯作者：
Kraft, Peter
影响因子：
16.6
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
通讯作者：
Tobin MD
影响因子：
30.8
作者：
Repapi, Emmanouela;Sayers, Ian;Tobin, Martin D.
通讯作者：
Tobin, Martin D.
DOI：
10.1161/circgenetics.108.829747
发表时间：
2009-02
期刊：
Circulation. Cardiovascular genetics
影响因子：
--
作者：
Psaty BM;O'Donnell CJ;Gudnason V;Lunetta KL;Folsom AR;Rotter JI;Uitterlinden AG;Harris TB;Witteman JC;Boerwinkle E;CHARGE Consortium
通讯作者：
CHARGE Consortium
影响因子：
2.1
作者：
Hutter, Carolyn M.;Mechanic, Leah E.;Chatterjee, Nilanjan;Kraft, Peter;Gillanders, Elizabeth M.
通讯作者：
Gillanders, Elizabeth M.