title: DNA methylation mediates the effect of exposure to prenatal maternal stress on cytokine production in children at age 13½  years: Project Ice Storm.
abstract: BACKGROUND
  Prenatal maternal stress (PNMS) is an important programming factor of postnatal immunity. We tested here the hypothesis that DNA methylation of genes in the NF-κB signaling pathway in T cells mediates the effect of objective PNMS on Th1 and Th2 cytokine production in blood from 13½ year olds who were exposed in utero to the 1998 Quebec ice storm.
  
  
  RESULTS
  Bootstrapping analyses were performed with 47 CpGs across a selection of 20 genes for Th1-type cytokines (IFN-γ and IL-2) and Th2-type cytokines (IL-4 and IL-13). Six CpGs in six different NF-κB signaling genes (PIK3CD, PIK3R2, NFKBIA, TRAF5, TNFRSF1B, and LTBR) remained as significant negative mediators of objective PNMS on IFN-γ secretion after correcting for multiple comparisons. However, no mediation effects on IL-2, IL-4 and IL-13 survived Bonferroni correction.
  
  
  CONCLUSIONS
  The present study provides preliminary evidence supporting the mediating role of DNA methylation in the association between objective aspects of PNMS and child immune states, favoring a Th2 shift.
authors.affiliation: Department of Psychiatry, McGill University and Douglas Hospital Research Centre, 6875 LaSalle Blvd, Montreal, Quebec H4H 1R3 Canada.
authors.forename: Lei
authors.initials: L
authors.lastname: Cao-Lei
authors.affiliation: Douglas Hospital Research Centre, Montreal, Quebec Canada.
authors.forename: Franz
authors.initials: F
authors.lastname: Veru
authors.affiliation: Douglas Hospital Research Centre, Montreal, Quebec Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Elgbeili
authors.affiliation: Department of Pharmacology and Therapeutics and Sackler Program for Epigenetics and Developmental Psychobiology, McGill University, Montreal, Quebec Canada.
authors.forename: Moshe
authors.initials: M
authors.lastname: Szyf
authors.affiliation: Douglas Hospital Research Centre, Montreal, Quebec Canada.
authors.forename: David P
authors.initials: DP
authors.lastname: Laplante
authors.affiliation: Department of Psychiatry, McGill University and Douglas Hospital Research Centre, 6875 LaSalle Blvd, Montreal, Quebec H4H 1R3 Canada.
authors.forename: Suzanne
authors.initials: S
authors.lastname: King
mesh_terms: D000293:Adolescent; D015331:Cohort Studies; D018899:CpG Islands; D016207:Cytokines / Q000235:genetics*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D018811:Maternal Exposure; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction; D013315:Stress, Psychological / Q000523:psychology*
chemical_list: D016207:Cytokines
keywords: Cytokines; DNA methylation; IFN-γ; Mediation effect; NF-κB signaling; Prenatal maternal stress