Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease

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dc.citation.firstpagee0152670en_US
dc.citation.issueNumber4en_US
dc.citation.journalTitlePLoS ONEen_US
dc.citation.volumeNumber11en_US
dc.contributor.authorWard-Caviness, Cavin K.en_US
dc.contributor.authorNeas, Lucas M.en_US
dc.contributor.authorBlach, Coletteen_US
dc.contributor.authorHaynes, Carol S.en_US
dc.contributor.authorLaRocque-Abramson, Karenen_US
dc.contributor.authorGrass, Elizabethen_US
dc.contributor.authorDowdy, Elaineen_US
dc.contributor.authorDevlin, Robert B.en_US
dc.contributor.authorDiaz-Sanchez, Daviden_US
dc.contributor.authorCascio, Wayne E.en_US
dc.contributor.authorMiranda, Marie Lynnen_US
dc.contributor.authorGregory, Simon G.en_US
dc.contributor.authorShah, Svati H.en_US
dc.contributor.authorKraus, William E.en_US
dc.contributor.authorHauser, Elizabeth R.en_US
dc.contributor.orgNational Center for Geospatial Medicineen_US
dc.date.accessioned2016-04-29T15:49:33Z
dc.date.available2016-04-29T15:49:33Z
dc.date.issued2016en_US
dc.description.abstractThere is a growing literature indicating that genetic variants modify many of the associations between environmental exposures and clinical outcomes, potentially by increasing susceptibility to these exposures. However, genome-scale investigations of these interactions have been rarely performed particularly in the case of air pollution exposures. We performed race-stratified genome-wide gene-environment interaction association studies on European-American (EA, N = 1623) and African-American (AA, N = 554) cohorts to investigate the joint influence of common single nucleotide polymorphisms (SNPs) and residential exposure to traffic (“traffic exposure”)—a recognized vascular disease risk factor—on peripheral arterial disease (PAD). Traffic exposure was estimated via the distance from the primary residence to the nearest major roadway, defined as the nearest limited access highways or major arterial. The rs755249-traffic exposure interaction was associated with PAD at a genome-wide significant level (P = 2.29x10-8) in European-Americans. Rs755249 is located in the 3’ untranslated region of BMP8A, a member of the bone morphogenic protein (BMP) gene family. Further investigation revealed several variants in BMP genes associated with PAD via an interaction with traffic exposure in both the EA and AA cohorts; this included interactions with non-synonymous variants in BMP2, which is regulated by air pollution exposure. The BMP family of genes is linked to vascular growth and calcification and is a novel gene family for the study of PAD pathophysiology. Further investigation of BMP8A using the Genotype Tissue Expression Database revealed multiple variants with nominally significant (P < 0.05) interaction P-values in our EA cohort were significant BMP8A eQTLs in tissue types highlight relevant for PAD such as rs755249 (tibial nerve, eQTL P = 3.6x10-6) and rs1180341 (tibial artery, eQTL P = 5.3x10-6). Together these results reveal a novel gene, and possibly gene family, associated with PAD via an interaction with traffic air pollution exposure. These results also highlight the potential for interactions studies, particularly at the genome scale, to reveal novel biology linking environmental exposures to clinical outcomes.en_US
dc.identifier.citationWard-Caviness, Cavin K., Neas, Lucas M., Blach, Colette, et al.. "Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease." <i>PLoS ONE,</i> 11, no. 4 (2016) Public Library of Science: e0152670. http://dx.doi.org/10.1371/journal.pone.0152670.
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0152670en_US
dc.identifier.urihttps://hdl.handle.net/1911/90375
dc.language.isoengen_US
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 the Creative Commons CC0 public domain dedication.en_US
dc.rights.urihttps://creativecommons.org/publicdomain/zero/1.0/en_US
dc.titleGenetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Diseaseen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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