title: Changes in DNA methylation over the growing season differ between North Carolina farmworkers and non-farmworkers.
abstract: OBJECTIVE
  The occupational risk to farmworkers, particularly chronic exposure to pesticides, is an acknowledged environmental and work-related health problem. Epigenetics has recently been shown to contribute to a number of complex diseases and traits, including measures of cognitive function and preclinical neurodegenerative disease. We sought to determine whether changes in DNA methylation existed between farmworker and non-farmworker populations and to identify the genes most likely involved in those changes.
  
  
  METHODS
  Eighty-three farmworkers and 60 non-farmworkers were selected from PACE4, a community-based, participatory research project comparing occupational exposures between immigrant Latino farmworker and non-farmworker manual workers. Measurements of DNA methylation were performed with the Infinium HumanMethylation450 BeadChip, at the beginning and end of the 2012 growing season. Bonferroni adjustment was used to identify significant findings (p = 1.03 × 10(-7), based on 485,000 tested methylation sites), although less stringent criteria (i.e., p ≤ 1 × 10(-6)) were used to identify sites of interest. Expression quantitative trait locus (eQTL) databases were used to help identify the most likely functional genes for each associated methylation site.
  
  
  RESULTS
  Methylation at 36 CpG sites, located in or near 72 genes, differed between the two groups (p ≤ 1 × 10(-6)). The difference between the two groups was generally due to an increase in methylation in the farmworkers and a slight decrease in methylation in the non-farmworkers. Enrichment was observed in several biological pathways, including those involved in the immune response, as well as growth hormone signaling, role of BRCA1 in DNA damage response, p70S6K signaling, and PI3K signaling in B lymphocytes.
  
  
  CONCLUSIONS
  We identified considerable changes in DNA methylation at 36 CpG sites over the growing season that differed between farmworkers and non-farmworkers. Dominant pathways included immune-related (HLA) processes, as well as a number of diverse biological systems. Further studies are necessary to determine which exposures or behaviors are responsible for the observed changes, and whether these changes eventually lead to disease-related phenotypes in this population.
authors.affiliation: Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA. tdhoward@wakehealth.edu.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Howard
authors.affiliation: Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA.
authors.forename: Fang-Chi
authors.initials: FC
authors.lastname: Hsu
authors.affiliation: Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA.
authors.forename: Haiying
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Quandt
authors.affiliation: Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA.
authors.forename: Jennifer W
authors.initials: JW
authors.lastname: Talton
authors.affiliation: Department of Family and Community Medicine, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: Summers
authors.affiliation: Department of Family and Community Medicine, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Arcury
mesh_terms: D000328:Adult; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D000067565:Farmers; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009657:North Carolina; D009784:Occupational Diseases / Q000235:genetics*; D012621:Seasons; D014171:Transients and Migrants
keywords: DNA methylation; Epigenetics; Farmworkers; Pesticides