Source: International Congress 2014 – Genes and environment in asthma and COPD
Disease area: Airway diseases

Abstract

BackgroundThus far, genome-wide association studies aiming to find novel susceptibility loci associated with chronic obstructive pulmonary disease (COPD) have largely disregarded environmental factors, like occupational exposures that may underlie disease development. Therefore we performed a genome-wide interaction study to identify novel susceptibility loci for occupational exposure to biological dust, mineral dust or gases and fumes in relation to the level of FEV₁.MethodsGenome-wide SNP-by occupational exposure interactions were identified in 12,400 subjects and verified in 1,436 subjects from two independent general population-based samples (figure 1). Additionally we assessed whether replicated SNPs were cis-acting expression quantitative trait loci (eQTL) in lung tissue.ResultsOf the 7 replicated SNPs that interacted with one of the occupational exposures, several were plausible candidates involved in biological pathways leading to impaired lung function, for example PCDH9 and GALNT13. Two of the 7 replicated SNPs were cis-acting eQTL associated with gene expression of neighboring genes PDE4D and TMEM176A in lung tissue (figure 1).ConclusionsWe identified several novel genes that interacted with occupational exposures on the level of FEV₁. Findings from the gene expression analysis provide additional support for a role of these genes in lung function impairment in subjects occupationally exposed.



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K. de Jong, J. Vonk, W. Timens, Y. Bossé, D. Sin, K. Hao, H. Kromhout, R. Vermeulen, D. Postma, M. Boezen (Groningen, Utrecht, Netherlands; Quebec, Vancouver, Canada; New York, United States Of America). Gene-by-occupational exposure interaction and gene expression analysis on the level of FEV₁. Eur Respir J 2014; 44: Suppl. 58, 2933

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