Evidence for large-scale gene-by-smoking interaction effects on pulmonary function

被引：36

作者：

Aschard, Hugues ^{[1
,2
]}

Tobin, Martin D. ^{[3
,4
]}

Hancock, Dana B. ^{[5
]}

Skurnik, David ^{[6
]}

Sood, Akshay ^{[7
]}

James, Alan ^{[8
,9
]}

Smith, Albert Vernon ^{[10
,11
]}

Manichaikul, Aniw ^{[12
,13
]}

Campbell, Archie ^{[14
,15
]}

Prins, Bram P. ^{[16
]}

Hayward, Caroline ^{[17
]}

Loth, Daanw

Porteous, David J. ^{[14
,15
]}

Strachan, David P. ^{[19
]}

Zeggini, Eleftheria ^{[16
]}

O'Connor, George T. ^{[20
,21
]}

Brusselle, Guy G. ^{[18
,22
,23
]}

Boezen, H. Marike ^{[24
,25
]}

Schulz, Holger ^{[26
,27
]}

Deary, Ian J. ^{[28
,29
]}

Hall, Ian P. ^{[30
]}

Rudan, Igor ^{[31
]}

Kaprio, Jaakko ^{[32
,33
,34
]}

Wilson, James F. ^{[17
,31
]}

Wilk, Jemma B. ^{[20
]}

Huffman, Jennifer E. ^{[17
]}

Zhao, Jing Hua ^{[35
,36
]}

de Jong, Kim ^{[24
,25
]}

Lyytikainen, Leo-Pekka ^{[37
,38
]}

Wain, Louise V. ^{[3
,4
]}

Jarvelin, Marjo-Riitta ^{[39
,40
,41
,42
]}

Kahonen, Mika ^{[43
,44
]}

Fornage, Myriam ^{[45
]}

Polasek, Ozren ^{[46
]}

Cassano, Patricia A. ^{[47
,48
]}

Barr, R. Graham ^{[49
]}

Rawal, Rajesh ^{[50
,51
,52
]}

Harris, Sarah E. ^{[14
,28
]}

Gharib, Sina A. ^{[53
]}

Enroth, Stefan ^{[54
]}

Heckbert, Susan R. ^{[55
]}

Lehtimaki, Terho ^{[37
,38
]}

Gyllensten, Ulf ^{[54
]}

Jackson, Victoria E. ^{[3
]}

Gudnason, Vilmundur

Tang, Wenbo ^{[47
,55
]}

Dupuis, Josee ^{[20
,56
]}

Artigas, Maria Soler ^{[3
]}

Joshi, Amit D. ^{[1
,2
,57
,58
]}

London, Stephanie J. ^{[59
]}

机构：

[1] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[2] Harvard TH Chan Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA USA

[3] Univ Leicester, Dept Hlth Sci, Genet Epidemiol Grp, Leicester, Leics, England

[4] Glenfield Hosp, Natl Inst Hlth Res, Leicester Resp Biomed Res Unit, Leicester, Leics, England

[5] Res Triangle Inst Int, Behav Hlth & Criminal Justice Res Div, Behav & Urban Hlth Program, Res Triangle Pk, NC USA

[6] Harvard Med Sch, Brigham & Women Hosp, Div Infect Dis, Boston, MA USA

[7] Univ New Mexico, Sch Med, Dept Internal Med, Div Pulm Crit Care & Sleep Med, Albuquerque, NM 87131 USA

[8] Sir Charles Gairdner Hosp, Dept Pulm Physiol & Sleep Med, Nedlands, WA, Australia

[9] Univ Western Australia, Sch Med & Pharmacol, Crawley, Australia

[10] Iceland Heart Assoc, Kopavogur, Iceland

[11] Univ Iceland, Fac Med, Reykjavik, Iceland

[12] Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA USA

[13] Univ Virginia, Dept Publ Hlth Sci, Div Biostat & Epidemiol, Charlottesville, VA USA

[14] Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland

[15] Univ Edinburgh, Ctr Genom & Expt Med, Generat Scotland, Edinburgh, Midlothian, Scotland

[16] Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England

[17] Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland

[18] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[19] St Georges Univ London, Populat Hlth Res Inst, London, England

[20] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA

[21] Boston Univ, Ctr Pulm, Sch Med, Dept Med, Boston, MA 02118 USA

[22] Ghent Univ Hosp, Dept Resp Med, Ghent, Belgium

[23] Erasmus MC, Dept Resp Med, Rotterdam, Netherlands

[24] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands

[25] Univ Groningen, Univ Med Ctr Groningen, Groningen Res Inst Asthma & COPD, Groningen, Netherlands

[26] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 1, Neuherberg, Germany

[27] Comprehens Pneumol Ctr Munich, German Ctr Lung Res, Munich, Germany

[28] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland

[29] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland

[30] Univ Nottingham, Queens Med Ctr, Div Resp Med, Nottingham, England

[31] Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland

[32] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland

[33] Univ Helsinki, Inst Mol Med, Helsinki, Finland

[34] Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland

[35] Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England

[36] Inst Metab Sci, Biomedical Campus, Cambridge, England

[37] Fimlab Labs, Dept Clin Chem, Tampere, Finland

[38] Univ Tampere, Sch Med, Dept Clin Chem, Tampere, Finland

[39] Imperial Coll London, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, Dept Epidemiol & Biostatist, London, England

[40] Univ Oulu, Fac Med, Ctr Life Course Epidemiol, Oulu, Finland

[41] Univ Oulu, Bioctr Oulu, Oulu, Finland

[42] Oulu Univ Hosp, Unit Primary Care, Oulu, Finland

[43] Univ Tampere, Dept Clin Physiol, Tampere, Finland

[44] Tampere Univ Hosp, Tampere, Finland

[45] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX 77030 USA

[46] Univ Split, Fac Med, Split, Croatia

[47] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA

[48] Weill Cornell Med Coll, Dept Healthcare Policy & Res, New York, NY USA

[49] Columbia Univ, Med Ctr, Dept Med & Epidemiol, New York, NY 10027 USA

[50] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, Neuherberg, Germany

来源：

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY | 2017年 / 46卷 / 03期

基金：

英国生物技术与生命科学研究理事会;

关键词：

FEV1/FVC; smoking; gene-environment interaction; genetic risk score; GENOME-WIDE ASSOCIATION; ENVIRONMENT INTERACTIONS; LUNG-FUNCTION; RISK; EPIDEMIOLOGY; OPPORTUNITIES; OBSTRUCTION; PREDICTION; FEV1/FVC; DISEASE;

D O I：

10.1093/ije/dyw318

中图分类号：

R1 [预防医学、卫生学];

学科分类号：

100235 [预防医学];

摘要：

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 (beta(int) = -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.

引用

页码：894 / 904

页数：11

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