Journal article

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

Hugues Aschard, Martin D Tobin, Dana B Hancock, David Skurnik, Akshay Sood, Alan James, Albert Vernon Smith, Aniw Manichaikul, Archie Campbell, Bram P Prins, Caroline Hayward, Daanw Loth, David J Porteous, David P Strachan, Eleftheria Zeggini, George T O'Connor, Guy G Brusselle, H Marike Boezen, Holger Schulz, Ian J Deary Show all

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY | OXFORD UNIV PRESS | Published : 2017

Abstract

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 FEV 1 (forced expiratory volume in 1 second) or FEV 1 /FVC (FEV 1 /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 s..

View full abstract

University of Melbourne Researchers

Grants


Awarded by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE


Awarded by NATIONAL HUMAN GENOME RESEARCH INSTITUTE


Awarded by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES


Awarded by NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES


Awarded by Biotechnology and Biological Sciences Research Council


Awarded by Economic and Social Research Council


Awarded by Medical Research Council


Awarded by Chief Scientist Office


Funding Acknowledgements

We thank the many colleagues who contributed to collection and phenotypic characterization of the clinical sampling and genotyping of the data. We especially thank those who kindly agreed to participate in the studies. H.A. was supported by R21HG007687. S.J.L. was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. The research undertaken by M.D.T., L.V.W. was partly funded by the National Institute for Health Research (NIHR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. A full list of studies and authors source of funding source and acknowledgements is provided in the Supplementary data. H.A., P.K., S.J.L., M.T., D.B.H. and A.J. were involved in designing the study. M.D.T., D.B.H., A.S., A.J., A.V.S., A.W.M., D.W.L., D.P.S., G.O.C., R.G.B., G.G.B., I.P.H., J.K.P., J.F.W., J.W., J.H.Z., K.d.J., L.V.W., M.S. ., H.M.B., M-R.J., M.F., P.A.C., S.A.G., S.R.H., V.G., W.T., S.J.L., I.R., O.P., J.E.H., C.H., A.C., D.J.P., S.E.H., I.J.D., S.E., U.G., LP.L., T.L., E.Z., B.P.P. and V.E.J. were involved in participant recruitment, sample collection or genotyping. H.A. performed analyses from the discovery study. H.A., V.E.J. and M.S.A. performed the replication analysis. H.A. drafted the paper, with substantial editorial input from P.K., S.J.L., J.D., D.S., M.T., D.B.H. and A.J. All authors have reviewed and approved the final draft. This material has not been published previously in a substantively similar form.