Research Article Advance Publication
Modification of the Association between PM10 and Lung Function Decline by Cadherin 13 Polymorphisms in the SAPALDIA Cohort: A Genome-Wide Interaction Analysis
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; http://dx.doi.org/10.1289/ehp.1307398.
Received: 20 July 2013
Accepted: 13 August 2014
Advance Publication: 15 August 2014
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.
CEHN December 2014 Article of the Month
“The Navigation Guide—Evidence-Based Medicine Meets Environmental Health: Integration of Animal and Human Evidence for PFOA Effects on Fetal Growth” (Environ Health Perspect; DOI:10.1289/ehp.1307923) has been selected by the Children’s Environmental Health Network (CEHN) as its December 2014 Article of the Month. These CEHN summaries discuss the potential policy implications of current children’s environmental health research.
Introducing Children’s Health Collection 2014
EHP’s fifth annual Children’s Health Collection is now available. The collection comprises abstracts of all relevant articles published in EHP from October 2013 through September 2014: peer-reviewed research articles, news features, Science Selections, and editorials.
ISEE 2014 Abstracts Now Available
EHP is pleased to present the abstracts for the 26th annual conference of the International Society for Environmental Epidemiology (ISEE), From Local to Global: Advancing Science for Policy in Environmental Health, held 24–28 August 2014 in Seattle, Washington.
Sign Up to Receive E-mail Alerts
Recent Advance Publications
Developmental Exposure to a Commercial PBDE Mixture: Effects on Protein Networks in the Cerebellum and Hippocampus of Rats
Attention Deficit/Hyperactivity Disorder and Childhood Autism in Association with Prenatal Exposure to Perfluoroalkyl Substances: A Nested Case–Control Study in the Danish National Birth Cohort
Autism Spectrum Disorder and Particulate Matter Air Pollution before, during, and after Pregnancy: A Nested Case–Control Analysis within the Nurses’ Health Study II Cohort
Comparative Effects of Di(n-Butyl) Phthalate Exposure on Fetal Germ Cell Development in the Rat and in Human Fetal Testis Xenografts
Interaction Effects of Temperature and Ozone on Lung Function and Markers of Systemic Inflammation, Coagulation, and Fibrinolysis: A Crossover Study of Healthy Young Volunteers