Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function

Hancock, D. B. and Soler, Artigas and Gharib, S. A. and Henry, A. and Manichaikul, A. and Ramasamy, A. and Loth, D. W. and Imboden, M. and Koch, B. and McArdle, W. and Smith, A. V. and Smolonska, J. and Sood, A. and Tang, W. and Wilk, J. B. and Zhai, G. and Zhao, J. H. and Aschard, H. and Burkart, K. M. and Curjuric, I. and Eijgelsheim, M. and Elliott, P. and Gu, X. and Harris, T. B. and Janson, C. and Homuth, G. and Hysi, P. and Liu, J. Z. and Loehr, L. R. and Lohman, K. and Loos, R. and Manning, A. K. and Marciante, K. D. and Obeidat, M. and Postma, D. and Aldrich, M. and Brusselle, G. G. and Chen, T. H. and Eiriksdottir, G. and Franceschini, N. and Heinrich, J. and Rotter, J. I. and Wijmenga, C. and Williams, O. D. and Bentley, A. R. and Hofman, A. and Laurie, C. and Lumley, T. and Morrison, A. C. and Joubert, B. R. and Rivadeneira, F. and Couper, D. J. and Kritchevsky, S. B. and Liu, Y. and Wjst, M. and Wain, L. V. and Vonk, J. M. and Uitterlinden, A. and Rochat, T. and Rich, S. S. and Psaty, B. M. and O'Connor, G. T. and North, K. E. and Mirel, D. B. and Meibohm, B. and Launer, L. J. and Khaw, K. T. and Hartikainen, A. L. and Hammond, C. J. and Gläser, S. and Marchini, J. and Kraft, P. and Wareham, N. J. and Völzke, H. and Stricker, B. H. C. and Spector, T. D. and Probst-Hensch, N. M. and Jarvis, D. and Jarvelin, M. R. and Heckbert, S. R. and Gudnason, V. and Boezen, H. M. and Barr, R. G. and Cassano, P. A. and Strachan, D. P. and Fornage, M. and Hall, I. P. and Dupuis, J. and Tobin, M. D. and London, S. J.. (2012) Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function. PLoS genetics, Vol. 8, H. 12 , e1003098.

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Official URL: http://edoc.unibas.ch/dok/A6094194

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Abstract

Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV(1)), and its ratio to forced vital capacity (FEV(1)/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV(1) and FEV(1)/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P(JMA = )5.00×10(-11)), HLA-DQB1 and HLA-DQA2 (smallest P(JMA = )4.35×10(-9)), and KCNJ2 and SOX9 (smallest P(JMA = )1.28×10(-8)) were associated with FEV(1)/FVC or FEV(1) in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.

Faculties and Departments:	09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology
UniBasel Contributors:	Curjuric, Ivan and Imboden, Medea
Item Type:	Article, refereed
Article Subtype:	Research Article
Publisher:	Public Library of Science
ISSN:	1553-7390
Note:	Publication type according to Uni Basel Research Database: Journal article
Language:	English
Related URLs:	Document Document
Identification Number:	pmid: 23284291 doi: 10.1371/journal.pgen.1003098
edoc DOI:	10.5451/unibas-ep28097
Last Modified:	31 Dec 2015 10:53
Deposited On:	19 Jul 2013 07:39

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