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Interaction with air pollution exposure for genetic loci associated with lung function

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conference contribution
posted on 22.05.2020, 09:15 by Louise Wain, Mesut Erzurumluoglu, Carl Melbourne, Dany Doiron, Kees De Hoogh, Martin Tobin, Anna Hansell

Air pollution has been found to be associated with reduced lung function; also 279 genetic signals of association with lung function have been identified that implicate multiple genes and pathways. In this study, we examined if any of these signals interact with air pollution measures NO2, PM2.5 and PM10.

In 259,389 unrelated European individuals from UK Biobank, we tested for a gene-environment interaction effect on lung function with NO2, PM2.5 and PM10 for each of the 279 signals. Lung function measures (FEV1, FEV1/FVC and FVC) were adjusted for sex, age, age2, height, and smoking, income and educational status, with adjustment for 15 principal components for fine-scale population structure. A significance threshold of P<1.8x10-4 (P<0.05 adjusted for 279 tests) was set.

We found statistically significant evidence for an interaction with PM2.5 on FEV1/FVC for rs10841302 on chromosome 12 (minor allele frequency=45.2%, interaction P=1.55x10-5). The SNP was also nominally significant for an interaction with PM10 and NO2 (P=5.2x10-4 and 2.3x10-3, respectively). This SNP did not show an interaction with tobacco smoke in a previous analysis. A further 16 SNPs had a nominally significant (P<0.05) interaction effect on lung function with air pollution but did not meet P<1.8x10-4.

The gene underlying the association of rs10841302 with lung function has not been determined but the SNP lies close to the AEBP2 gene which encodes AE Binding Protein 2, a transcriptional repressor which may have a role in histone methylation. Identification and characterisation of genes whose effect is influenced by air pollution exposure will enable us to understand how the environment influences respiratory health.

History

Citation

Louise Wain, Mesut Erzurumluoglu, Carl Melbourne, Dany Doiron, Kees De Hoogh, Martin Tobin, Anna Hansell European Respiratory Journal 2019 54: PA5395; DOI: 10.1183/13993003.congress-2019.PA5395

Source

European-Respiratory-Society (ERS) International Congress

Version

AM (Accepted Manuscript)

Published in

European Respiratory Journal

Volume

54

Issue

suppl 63

Pagination

PA5395 (2)

Publisher

European Respiratory Society: ERJ

issn

0903-1936

eissn

1399-3003

Copyright date

2019

Notes

Abstract only

Spatial coverage

Madrid, SPAIN

Temporal coverage: start date

28/09/2019

Temporal coverage: end date

02/10/2019

Language

en