Association of distance to swine concentrated animal feeding operations with immune-mediated diseases: An exploratory gene-environment study

Montserrat Ayala-Ramirez; Nathaniel MacNell; Lucy E. McNamee; John A. McGrath; Farida S. Akhtari; Matthew D. Curry; Askia K. Dunnon; Michael B. Fessler; Stavros Garantziotis; Christine G. Parks; David C. Fargo; Charles P. Schmitt; Alison A. Motsinger-Reif; Janet E. Hall; Frederick W. Miller; Shepherd H. Schurman

Environment International (Jan 2023)

Association of distance to swine concentrated animal feeding operations with immune-mediated diseases: An exploratory gene-environment study

Montserrat Ayala-Ramirez,
Nathaniel MacNell,
Lucy E. McNamee,
John A. McGrath,
Farida S. Akhtari,
Matthew D. Curry,
Askia K. Dunnon,
Michael B. Fessler,
Stavros Garantziotis,
Christine G. Parks,
David C. Fargo,
Charles P. Schmitt,
Alison A. Motsinger-Reif,
Janet E. Hall,
Frederick W. Miller,
Shepherd H. Schurman

Affiliations

Montserrat Ayala-Ramirez: Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA
Nathaniel MacNell: Social and Scientific Systems, 505 Emperor Blvd Suite 400, Durham, NC 27703, USA
Lucy E. McNamee: Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA
John A. McGrath: Social and Scientific Systems, 505 Emperor Blvd Suite 400, Durham, NC 27703, USA
Farida S. Akhtari: Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA
Matthew D. Curry: Social and Scientific Systems, 505 Emperor Blvd Suite 400, Durham, NC 27703, USA
Askia K. Dunnon: Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA
Michael B. Fessler: Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, Mail Drop D2-01, Durham, NC 27709, USA
Stavros Garantziotis: Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, BG 109 RM 109 MSC CU-01, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA
Christine G. Parks: Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, Mail Drop A3-05, Durham, NC 27709, USA
David C. Fargo: Office of Scientific Computing, National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, Mail Drop B3-01, Durham, NC 27709, USA
Charles P. Schmitt: Office of Data Science, National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, Mail Drop K2-02, Durham, NC 27709, USA
Alison A. Motsinger-Reif: PEGS Co-PI, Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, 111 T.W. Alexander Drive, RTP 101, Research Triangle Park, NC 27709, USA
Janet E. Hall: PEGS Co-PI, Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, BG 101 RM A222 MSC A2-03. 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA
Frederick W. Miller: Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, 111 T.W. Alexander Drive, RTP 101 David P. Rall Building, Research Triangle Park, NC 27709, USA
Shepherd H. Schurman: Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA; Corresponding authors at: Clinical Research Unit, National Institute on Aging, National Institutes of Health, Harbor BG Rm SM528, 3001 S. Hanover St, Baltimore, MD 21225, USA.

Journal volume & issue: Vol. 171
p. 107687

Abstract

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Background: Concentrated animal feeding operations (CAFOs) are a source of environmental pollution and have been associated with a variety of health outcomes. Immune-mediated diseases (IMD) are characterized by dysregulation of the normal immune response and, while they may be affected by gene and environmental factors, their association with living in proximity to a CAFO is unknown. Objectives: We explored gene, environment, and gene-environment (GxE) relationships between IMD, CAFOs, and single nucleotide polymorphisms (SNPs) of prototypical xenobiotic response genes AHR, ARNT, and AHRR and prototypical immune response gene PTPN22. Methods: The exposure analysis cohort consisted of 6,464 participants who completed the Personalized Environment and Genes Study Health and Exposure Survey and a subset of 1,541 participants who were genotyped. We assessed the association between participants’ residential proximity to a CAFO in gene, environment, and GxE models. We recombined individual associations in a transethnic model using METAL meta-analysis. Results: In White participants, ARNT SNP rs11204735 was associated with autoimmune diseases and rheumatoid arthritis (RA), and ARNT SNP rs1889740 was associated with RA. In a transethnic genetic analysis, ARNT SNPs rs11204735 and rs1889740 and PTPN22 SNP rs2476601 were associated with autoimmune diseases and RA. In participants living closer than one mile to a CAFO, the log-distance to a CAFO was associated with autoimmune diseases and RA. In a GxE interaction model, White participants with ARNT SNPs rs11204735 and rs1889740 living closer than eight miles to a CAFO had increased odds of RA and autoimmune diseases, respectively. The transethnic model revealed similar GxE interactions. Conclusions: Our results suggest increased risk of autoimmune diseases and RA in those living in proximity to a CAFO and a potential role of the AHR-ARNT pathway in conferring risk. We also report the first association of ARNT SNPs rs11204735 and rs1889740 with RA. Our findings, if confirmed, could allow for novel genetically-targeted or other preventive approaches for certain IMD.

Published in Environment International

ISSN: 0160-4120 (Print)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Geography. Anthropology. Recreation: Environmental sciences
Website: https://www.journals.elsevier.com/environment-international

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