A genome-wide trans-ethnic interaction study links theﾠPIGR-FCAMRﾠlocus to coronary atherosclerosis via interactions between genetic variants and residential exposure to traffic

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dc.citation.articleNumbere0173880
dc.citation.issueNumber3
dc.citation.journalTitlePLoS ONE
dc.citation.volumeNumber12
dc.contributor.authorWard-Caviness, Cavin K.
dc.contributor.authorNeas, Lucas M.
dc.contributor.authorBlach, Colette
dc.contributor.authorHaynes, Carol S.
dc.contributor.authorLaRocque-Abramson, Karen
dc.contributor.authorGrass, Elizabeth
dc.contributor.authorDowdy, Z. Elaine
dc.contributor.authorDevlin, Robert B.
dc.contributor.authorDiaz-Sanchez, David
dc.contributor.authorCascio, Wayne E.
dc.contributor.authorMiranda, Marie Lynn
dc.contributor.authorGregory, Simon G.
dc.contributor.authorShah, Svati H.
dc.contributor.authorKraus, William E.
dc.contributor.authorHauser, Elizabeth R.
dc.date.accessioned2017-05-05T19:00:53Z
dc.date.available2017-05-05T19:00:53Z
dc.date.issued2017
dc.description.abstractAir 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.
dc.identifier.citationWard-Caviness, Cavin K., Neas, Lucas M., Blach, Colette, et al.. "A genome-wide trans-ethnic interaction study links theﾠPIGR-FCAMRﾠlocus to coronary atherosclerosis via interactions between genetic variants and residential exposure to traffic." <i>PLoS ONE,</i> 12, no. 3 (2017) Public Library of Science: https://doi.org/10.1371/journal.pone.0173880.
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0173880
dc.identifier.urihttps://hdl.handle.net/1911/94194
dc.language.isoeng
dc.publisherPublic Library of Science
dc.rightsThis is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under theﾠCreative Commons CC0ﾠpublic domain dedication.
dc.rights.urihttps://creativecommons.org/publicdomain/zero/1.0/
dc.titleA genome-wide trans-ethnic interaction study links theﾠPIGR-FCAMRﾠlocus to coronary atherosclerosis via interactions between genetic variants and residential exposure to traffic
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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