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

Publication ,  Journal Article
Ward-Caviness, CK; Neas, LM; Blach, C; Haynes, CS; LaRocque-Abramson, K; Grass, E; Dowdy, E; Devlin, RB; Diaz-Sanchez, D; Cascio, WE; Shah, SH ...
Published in: PLoS One
2016

There 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.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2016

Volume

11

Issue

4

Start / End Page

e0152670

Location

United States

Related Subject Headings

  • Transportation
  • Polymorphism, Single Nucleotide
  • Peripheral Arterial Disease
  • Middle Aged
  • Male
  • Humans
  • Housing
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • General Science & Technology
 

Citation

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Ward-Caviness, C. K., Neas, L. M., Blach, C., Haynes, C. S., LaRocque-Abramson, K., Grass, E., … Hauser, E. R. (2016). Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease. PLoS One, 11(4), e0152670. https://doi.org/10.1371/journal.pone.0152670
Ward-Caviness, Cavin K., Lucas M. Neas, Colette Blach, Carol S. Haynes, Karen LaRocque-Abramson, Elizabeth Grass, Elaine Dowdy, et al. “Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease.PLoS One 11, no. 4 (2016): e0152670. https://doi.org/10.1371/journal.pone.0152670.
Ward-Caviness CK, Neas LM, Blach C, Haynes CS, LaRocque-Abramson K, Grass E, et al. Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease. PLoS One. 2016;11(4):e0152670.
Ward-Caviness, Cavin K., et al. “Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease.PLoS One, vol. 11, no. 4, 2016, p. e0152670. Pubmed, doi:10.1371/journal.pone.0152670.
Ward-Caviness CK, Neas LM, Blach C, Haynes CS, LaRocque-Abramson K, Grass E, Dowdy E, Devlin RB, Diaz-Sanchez D, Cascio WE, Lynn Miranda M, Gregory SG, Shah SH, Kraus WE, Hauser ER. Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease. PLoS One. 2016;11(4):e0152670.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2016

Volume

11

Issue

4

Start / End Page

e0152670

Location

United States

Related Subject Headings

  • Transportation
  • Polymorphism, Single Nucleotide
  • Peripheral Arterial Disease
  • Middle Aged
  • Male
  • Humans
  • Housing
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • General Science & Technology