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Genes and pathways underlying susceptibility to impaired lung function in the context of environmental tobacco smoke exposure

de Jong, K. and Vonk, J. M. and Imboden, M. and Lahousse, L. and Hofman, A. and Brusselle, G. G. and Probst-Hensch, N. M. and Postma, D. S. and Boezen, H. M.. (2017) Genes and pathways underlying susceptibility to impaired lung function in the context of environmental tobacco smoke exposure. Respiratory research, 18 (1). p. 142.

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Official URL: http://edoc.unibas.ch/55889/

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Abstract

Studies aiming to assess genetic susceptibility for impaired lung function levels upon exposure to environmental tobacco smoke (ETS) have thus far focused on candidate-genes selected based on a-priori knowledge of potentially relevant biological pathways, such as glutathione S-transferases and ADAM33. By using a hypothesis-free approach, we aimed to identify novel susceptibility loci, and additionally explored biological pathways potentially underlying this susceptibility to impaired lung function in the context of ETS exposure.; Genome-wide interactions of single nucleotide polymorphism (SNP) by ETS exposure (0 versus ≥1 h/day) in relation to the level of forced expiratory volume in one second (FEV1) were investigated in 10,817 subjects from the Dutch LifeLines cohort study, and verified in subjects from the Swiss SAPALDIA study (n = 1276) and the Dutch Rotterdam Study (n = 1156). SNP-by-ETS exposure p-values obtained from the identification analysis were used to perform a pathway analysis.; Fourty Five SNP-by-ETS exposure interactions with p-values <10(-4) were identified in the LifeLines study, two being replicated with nominally significant p-values (<0.05) in at least one of the replication cohorts. Three pathways were enriched in the pathway-level analysis performed in the identification cohort LifeLines, i.E. the apoptosis, p38 MAPK and TNF pathways.; This unique, first genome-wide gene-by-ETS interaction study on the level of FEV1 showed that pathways previously implicated in chronic obstructive pulmonary disease (COPD), a disease characterized by airflow obstruction, may also underlie susceptibility to impaired lung function in the context of ETS exposure.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Imboden, Medea and Probst Hensch, Nicole
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:BioMed Central
ISSN:1465-9921
e-ISSN:1465-993X
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:05 Oct 2017 07:33
Deposited On:05 Oct 2017 07:33

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