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Research Article Advance Publication

Environ Health Perspect; DOI:10.1289/ehp.1307398

Modification of the Association between PM10 and Lung Function Decline by Cadherin 13 Polymorphisms in the SAPALDIA Cohort: A Genome-Wide Interaction Analysis

Medea Imboden,1,2 Ashish Kumar,1,2,3 Ivan Curjuric,1,2 Martin Adam,1,2 Gian Andri Thun,1,2 Margot Haun,4 Ming-Yi Tsai,1,2 Marco Pons,5 Robert Bettschart,6 Alexander Turk,7 Thierry Rochat,8 Nino Künzli,1,2 Christian Schindler,1,2 Florian Kronenberg,4 and Nicole M. Probst-Hensch1,2
Author Affiliations close
1Swiss Tropical and Public Health Institute, Basel, Switzerland; 2University of Basel, Switzerland; 3Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; 4Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria; 5Division of Pulmonary Medicine, Regional Hospital of Lugano, Lugano, Switzerland; 6Lungenzentrum, Hirslanden Klinik, Aarau, Switzerland; 7Zürcher Höhenklinik, Wald, Faltigberg-Wald, Switzerland; 8Division of Pulmonary Medicine, University Hospitals of Geneva, Geneva, Switzerland
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This EHP Advance Publication article has been peer-reviewed, revised, and accepted for publication. EHP Advance Publication articles are completely citable using the DOI number assigned to the article. This document will be replaced with the copyedited and formatted version as soon as it is available. Through the DOI number used in the citation, you will be able to access this document at each stage of the publication process.

Citation: 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. 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;

Received: 20 July 2013
Accepted: 13 August 2014
Advance Publication: 15 August 2014

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Background: 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.

Objectives: 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.

Methods: A two-stage genome-wide interaction study was performed. The discovery (N=763) and replication samples (N=3,896) were derived from the multi-centric 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 endpoint. Multivariate linear regression analyses were used to identify potential multiplicative interactions between genotypes and 11-year cumulative PM10 exposure.

Results: 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.

Conclusions: 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.

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