{"doi":"10.1093/aje/kwaa227","title":"Genome-Wide Gene-by-Smoking Interaction Study of Chronic Obstructive Pulmonary Disease","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.","journal":"American Journal of Epidemiology","year":2020,"id":61174,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":58,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8884,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":24853,"name":"Dmitry Prokopenko","orcid":"0000-0002-1844-5652","position":1,"is_corresponding":false},{"id":24868,"name":"Phuwanat Sakornsakolpat","orcid":"0000-0002-4308-0974","position":2,"is_corresponding":false},{"id":267144,"name":"Brian D. Hobbs","orcid":"0000-0001-9564-0745","position":3,"is_corresponding":false},{"id":14698,"name":"Sharon M. Lutz","orcid":"0000-0002-1515-9431","position":4,"is_corresponding":false},{"id":268136,"name":"John E. Hokanson","orcid":"0000-0003-0500-6068","position":5,"is_corresponding":false},{"id":70435,"name":"Louise V. Wain","orcid":"0000-0003-4951-1867","position":6,"is_corresponding":false},{"id":323168,"name":"Carl Melbourne","orcid":"0000-0001-7216-4547","position":7,"is_corresponding":false},{"id":70431,"name":"Nick Shrine","orcid":"0000-0003-3641-4371","position":8,"is_corresponding":false},{"id":70434,"name":"Martin D. Tobin","orcid":"0000-0002-3596-7874","position":9,"is_corresponding":false},{"id":25018,"name":"Edwin K. Silverman","orcid":"0000-0002-3641-3822","position":10,"is_corresponding":false},{"id":218537,"name":"Michael H. Cho","orcid":"0000-0002-4907-1657","position":11,"is_corresponding":false},{"id":24943,"name":"Terri H. Beaty","orcid":"0000-0002-7644-1705","position":12,"is_corresponding":false},{"id":289838,"name":"Woori Kim","orcid":"0000-0002-7951-9280","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-18T21:09:27.985420Z","pmid":"33106845","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}