Genome-wide interaction study of early-life smoking exposure on time-to-asthma onset in childhood

Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology
Pierre-Emmanuel SugierEmmanuelle Bouzigon

Abstract

Asthma, a heterogeneous disease with variable age of onset, results from the interplay between genetic and environmental factors. Early-life tobacco smoke (ELTS) exposure is a major asthma risk factor. Only a few genetic loci have been reported to interact with ELTS exposure in asthma. Our aim was to identify new loci interacting with ELTS exposure on time-to-asthma onset (TAO) in childhood. We conducted genome-wide interaction analyses of ELTS exposure on time-to-asthma onset in childhood in five European-ancestry studies (totalling 8273 subjects) using Cox proportional-hazard model. The results of all five genome-wide analyses were meta-analysed. The 13q21 locus showed genome-wide significant interaction with ELTS exposure (P = 4.3 × 10-8 for rs7334050 within KLHL1 with consistent results across the five studies). Suggestive interactions (P < 5 × 10-6 ) were found at three other loci: 20p12 (rs13037508 within MACROD2; P = 4.9 × 10-7 ), 14q22 (rs7493885 near NIN; P = 2.9 × 10-6 ) and 2p22 (rs232542 near CYP1B1; P = 4.1 × 10-6 ). Functional annotations and the literature showed that the lead SNPs at these four loci influence DNA methylation in the blood and are located nearby CpG sites reported to be associated with exposure to...Continue Reading

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Jan 28, 2020·Current Opinion in Allergy and Clinical Immunology·Korneliusz GolebskiUNKNOWN PERMEABLE consortium
Oct 9, 2020·Chinese Medical Journal·Hong-Lei ShiJing Liu
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