title: A genome-wide trans-ethnic interaction study links the PIGR-FCAMR locus to coronary atherosclerosis via interactions between genetic variants and residential exposure to traffic.
abstract: Air pollution is a worldwide contributor to cardiovascular disease mortality and morbidity. Traffic-related air pollution is a widespread environmental exposure and is associated with multiple cardiovascular outcomes such as coronary atherosclerosis, peripheral arterial disease, and myocardial infarction. Despite the recognition of the importance of both genetic and environmental exposures to the pathogenesis of cardiovascular disease, studies of how these two contributors operate jointly are rare. We performed a genome-wide interaction study (GWIS) to examine gene-traffic exposure interactions associated with coronary atherosclerosis. Using race-stratified cohorts of 538 African-Americans (AA) and 1562 European-Americans (EA) from a cardiac catheterization cohort (CATHGEN), we identify gene-by-traffic exposure interactions associated with the number of significantly diseased coronary vessels as a measure of chronic atherosclerosis. We found five suggestive (P<1x10-5) interactions in the AA GWIS, of which two (rs1856746 and rs2791713) replicated in the EA cohort (P < 0.05). Both SNPs are in the PIGR-FCAMR locus and are eQTLs in lymphocytes. The protein products of both PIGR and FCAMR are implicated in inflammatory processes. In the EA GWIS, there were three suggestive interactions; none of these replicated in the AA GWIS. All three were intergenic; the most significant interaction was in a regulatory region associated with SAMSN1, a gene previously associated with atherosclerosis and B cell activation. In conclusion, we have uncovered several novel genes associated with coronary atherosclerosis in individuals chronically exposed to increased ambient concentrations of traffic air pollution. These genes point towards inflammatory pathways that may modify the effects of air pollution on cardiovascular disease risk.
authors.affiliation: Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, United States of America.|Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany.|National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Chapel Hill, NC, United States of America.
authors.forename: Cavin K
authors.identifier: http://orcid.org/0000-0002-6322-4349
authors.initials: CK
authors.lastname: Ward-Caviness
authors.affiliation: National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Chapel Hill, NC, United States of America.
authors.forename: Lucas M
authors.initials: LM
authors.lastname: Neas
authors.affiliation: Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, United States of America.
authors.forename: Colette
authors.initials: C
authors.lastname: Blach
authors.affiliation: Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, United States of America.
authors.forename: Carol S
authors.initials: CS
authors.lastname: Haynes
authors.affiliation: Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, United States of America.
authors.forename: Karen
authors.initials: K
authors.lastname: LaRocque-Abramson
authors.affiliation: Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Grass
authors.affiliation: Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, United States of America.
authors.forename: Z Elaine
authors.initials: ZE
authors.lastname: Dowdy
authors.affiliation: National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Chapel Hill, NC, United States of America.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Devlin
authors.affiliation: National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Chapel Hill, NC, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Diaz-Sanchez
authors.affiliation: National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Chapel Hill, NC, United States of America.
authors.forename: Wayne E
authors.initials: WE
authors.lastname: Cascio
authors.affiliation: National Center for Geospatial Medicine, Rice University, Houston, TX, United States of America.
authors.forename: Marie Lynn
authors.initials: ML
authors.lastname: Miranda
authors.affiliation: Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, United States of America.
authors.forename: Simon G
authors.initials: SG
authors.lastname: Gregory
authors.affiliation: Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, United States of America.|Division of Cardiology, Duke University School of Medicine, Durham, NC, United States of America.
authors.forename: Svati H
authors.initials: SH
authors.lastname: Shah
authors.affiliation: Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, United States of America.|Division of Cardiology, Duke University School of Medicine, Durham, NC, United States of America.
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
authors.affiliation: Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, United States of America.|Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, United States of America.|Cooperative Studies Program Epidemiology Center-Durham, Veterans Affairs Medical Center, Durham, NC, United States of America.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Hauser
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000276:immunology; D001741:Black or African American; D000368:Aged; D000397:Air Pollution / Q000009:adverse effects*; D050197:Atherosclerosis / Q000208:ethnology / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D006328:Cardiac Catheterization; D003324:Coronary Artery Disease / Q000208:ethnology / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D059647:Gene-Environment Interaction; D056426:Genetic Loci; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D040641:Quantitative Trait Loci; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000276:immunology; D011961:Receptors, Fc / Q000235:genetics* / Q000276:immunology; D001335:Vehicle Emissions; D044465:White People
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D011961:Receptors, Fc; D001335:Vehicle Emissions; C512828:OSCAR protein, human; C435526:SAMSN1 protein, human; C526790:Fcalpha-mu receptor, human