title: Distributional changes in gene-specific methylation associated with temperature.
abstract: Temperature has been related to mean differences in DNA methylation. However, heterogeneity in these associations may exist across the distribution of methylation outcomes. This study examined whether the association between three-week averaged of temperature and methylation differs across quantiles of the methylation distributions in nine candidate genes. We measured gene-specific blood methylation repeatedly in 777 elderly men participating in the Normative Aging Study (1999-2010). We fit quantile regressions for longitudinal data to investigate whether the associations of temperature on methylation (expressed as %5mC) varied across the distribution of the methylation outcomes. We observed heterogeneity in the associations of temperature across percentiles of methylation in F3, TLR-2, CRAT, iNOS, and ICAM-1 genes. For instance, an increase in three-week temperature exposure was associated with a longer left-tail of the F3 methylation distribution. A 5°C increase in temperature was associated with a 0.15%5mC (95% confidence interval (CI): -0.27,-0.04) decrease on the 20th quantile of F3 methylation, but was not significantly related to the 80th quantile of this distribution (Estimate:0.06%5mC, 95%CI: -0.22, 0.35). Individuals with low values of F3, TLR-2, CRAT, and iNOS methylation, as well as a high value of ICAM-1 methylation, may be more susceptible to temperature effects on systemic inflammation.
authors.affiliation: Department of Statistics, Faculty of Arts and Science, Harvard University, Cambridge, MA, USA.
authors.forename: Marie-Abele C
authors.initials: MC
authors.lastname: Bind
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Brent A
authors.initials: BA
authors.lastname: Coull
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Baccarelli
authors.affiliation: Center of Molecular and Genetic Epidemiology, Department of Clinical Sciences and Community Health, Università degli Studi di Milano and Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Tarantini
authors.affiliation: Center of Molecular and Genetic Epidemiology, Department of Clinical Sciences and Community Health, Università degli Studi di Milano and Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Cantone
authors.affiliation: VA Normative Aging Study, VA Boston Healthcare System and the Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Pantel
authors.initials: P
authors.lastname: Vokonas
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001774:Blood Chemical Analysis; D001900:Boston; D003080:Cold Temperature; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006358:Hot Temperature; D006801:Humans; D008297:Male; D008875:Middle Aged
keywords: DNA methylation; Quantile regression; Susceptibility; Temperature