| Title: | Genome-Wide Gene-by-Smoking Interaction Study of Chronic Obstructive Pulmonary Disease |
| Journal: | American Journal of Epidemiology |
| Published: | 27 Oct 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33106845/ |
| DOI: | https://doi.org/10.1093/aje/kwaa227 |
| URL: | https://academic.oup.com/aje/article-pdf/190/5/875/37798740/kwaa227.pdf |
| Citations: | 27 (12 in last 2 years) as of 8 Aug 2024 |
Publication 5056
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Abstract
Risk of chronic obstructive pulmonary disease (COPD) is determined by both cigarette smoking and genetic susceptibility, but little is known about gene-by-smoking interactions. We performed a genome-wide association analysis of 179,689 controls and 21,077 COPD cases from UK Biobank subjects of European ancestry recruited from 2006 to 2010, considering genetic main effects and gene-by-smoking interaction effects simultaneously (2-degrees-of-freedom (df) test) as well as interaction effects alone (1-df interaction test). We sought to replicate significant results in COPDGene (United States, 2008-2010) and SpiroMeta Consortium (multiple countries, 1947-2015) data. We considered 2 smoking variables: 1) ever/never and 2) current/noncurrent. In the 1-df test, we identified 1 genome-wide significant locus on 15q25.1 (cholinergic receptor nicotinic β4 subunit, or CHRNB4) for ever- and current smoking and identified PI*Z allele (rs28929474) of serpin family A member 1 (SERPINA1) for ever-smoking and 3q26.2 (MDS1 and EVI1 complex locus, or MECOM) for current smoking in an analysis of previously reported COPD loci. In the 2-df test, most of the significant signals were also significant for genetic marginal effects, aside from 16q22.1 (sphingomyelin phosphodiesterase 3, or SMPD3) and 19q13.2 (Egl-9 family hypoxia inducible factor 2, or EGLN2). The significant effects at 15q25.1 and 19q13.2 loci, both previously described in prior genome-wide association studies of COPD or smoking, were replicated in COPDGene and SpiroMeta. We identified interaction effects at previously reported COPD loci; however, we failed to identify novel susceptibility loci.</p>
13 Keywords
- Case-Control Studies
- Female
- Gene-Environment Interaction
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Male
- Middle Aged
- Pulmonary Disease, Chronic Obstructive
- Respiratory Function Tests
- Smoking
- United Kingdom
- White People
13 Authors
- Woori Kim
- Dmitry Prokopenko
- Phuwanat Sakornsakolpat
- Brian D Hobbs
- Sharon M Lutz
- John E Hokanson
- Louise V Wain
- Carl A Melbourne
- Nick Shrine
- Martin D Tobin
- Edwin K Silverman
- Michael H Cho
- Terri H Beaty
Enabling scientific discoveries that improve human health