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Modification of the association between PM10 and lung function decline by cadherin 13 polymorphisms in the SAPALDIA cohort : a genome-wide interaction analysis

Imboden, Medea and Kumar, Ashish and Curjuric, Ivan and Adam, Martin and Thun, Gian Andri and Haun, Margot and Tsai, Ming-Yi and Pons, Marco and Bettschart, Robert and Turk, Alexander and Rochat, Thierry and Künzli, Nino and Schindler, Christian and Kronenberg, Florian and Probst-Hensch, Nicole M.. (2015) Modification of the association between PM10 and lung function decline by cadherin 13 polymorphisms in the SAPALDIA cohort : a genome-wide interaction analysis. Environmental Health Perspectives, 123 (1). pp. 72-79.

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Official URL: http://edoc.unibas.ch/dok/A6338836

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Abstract

Both air pollution and genetic variation have been shown to affect lung function. Their interaction has not been studied on a genome-wide scale to date.; We aimed to identify, in an agnostic fashion, genes that modify the association between long-term air pollution exposure and annual lung function decline in an adult population-based sample.; A two-stage genome-wide interaction study was performed. The discovery (n = 763) and replication (n = 3,896) samples were derived from the multi-center SAPALDIA cohort (Swiss Cohort Study on Air Pollution and Lung Disease in Adults). Annual rate of decline in the forced mid-expiratory flow (FEF25-75%) was the main end point. Multivariate linear regression analyses were used to identify potential multiplicative interactions between genotypes and 11-year cumulative PM10 exposure.; We identified a cluster of variants intronic to the CDH13 gene as the only locus with genome-wide significant interactions. The strongest interaction was observed for rs2325934 (p = 8.8 × 10-10). Replication of the interaction between this CDH13 variant and cumulative PM10 exposure on annual decline in FEF25-75% was successful (p = 0.008). The interaction was not sensitive to adjustment for smoking or body weight.; CDH13 is functionally linked to the adipokine adiponectin, an inflammatory regulator. Future studies need to confirm the interaction and assess how the result relates to previously observed interactions between air pollution and obesity on respiratory function.; Imboden M, Kumar A, Curjuric I, Adam M, Thun GA, Haun M, Tsai MY, Pons M, Bettschart R, Turk A, Rochat T, Künzli N, Schindler C, Kronenberg F, Probst-Hensch NM. 2015. Modification of the association between PM10 and lung function decline by cadherin 13 polymorphisms in the SAPALDIA cohort: a genome-wide interaction analysis. Environ Health Perspect 123:72-79; http://dx.doi.org/10.1289/ehp.1307398.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology > Air Pollution and Health (Künzli)
03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Air Pollution and Health (Künzli)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Biostatistics > Biostatistics Frequentist Modelling
UniBasel Contributors:Imboden, Medea and Künzli, Nino and Probst Hensch, Nicole and Kumar, Ashish and Kumar, Ashish and Thun, Gian Andri and Adam, Martin and Thun, Gian Andri and Tsai, Ming and Schindler, Christian
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Institute of Environmental Health Sciences
ISSN:0091-6765
e-ISSN:1552-9924
Note:Publication type according to Uni Basel Research Database: Journal article -- Reproduced with permission from Environmental Health Perspectives
Language:English
Identification Number:
Last Modified:31 Aug 2017 07:30
Deposited On:06 Feb 2015 09:59

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