title: Adiposity is associated with DNA methylation profile in adipose tissue.
abstract: BACKGROUND
  Adiposity is a risk factor for type 2 diabetes and cardiovascular disease, suggesting an important role for adipose tissue in the development of these conditions. The epigenetic underpinnings of adiposity are not well understood, and studies of DNA methylation in relation to adiposity have rarely focused on target adipose tissue. Objectives were to evaluate whether genome-wide DNA methylation profiles in subcutaneous adipose tissue and peripheral blood leukocytes are associated with measures of adiposity, including central fat mass, body fat distribution and body mass index.
  
  
  METHODS
  Participants were 106 men and women (mean age 47 years) from the New England Family Study. DNA methylation was evaluated using the Infinium HumanMethylation450K BeadChip. Adiposity phenotypes included dual-energy X-ray absorptiometry-assessed android fat mass, android:gynoid fat ratio and trunk:limb fat ratio, as well as body mass index.
  
  
  RESULTS
  Adipose tissue genome-wide DNA methylation profiles were associated with all four adiposity phenotypes, after adjusting for race, sex and current smoking (omnibus p-values <0.001). After further adjustment for adipose cell-mixture effects, associations with android fat mass, android:gynoid fat ratio, and trunk:limb fat ratio remained. In gene-specific analyses, adiposity phenotypes were associated with adipose tissue DNA methylation in several genes that are biologically relevant to the development of adiposity, such as AOC3, LIPE, SOD3, AQP7 and CETP. Blood DNA methylation profiles were not associated with adiposity, before or after adjustment for blood leukocyte cell mixture effects.
  
  
  CONCLUSIONS
  Findings show that DNA methylation patterns in adipose tissue are associated with adiposity.
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA, gagha@hsph.harvard.edu.
authors.forename: Golareh
authors.initials: G
authors.lastname: Agha
authors.affiliation: College of Public Health and Human Sciences, Oregon State University, Corvallis, OR, USA.
authors.forename: E Andres
authors.initials: EA
authors.lastname: Houseman
authors.affiliation: Department of Epidemiology, Brown University School of Public Health, Providence, RI, USA, Department of Pathology and Laboratory Medicine and.
authors.forename: Karl T
authors.initials: KT
authors.lastname: Kelsey
authors.affiliation: Department of Epidemiology, Brown University School of Public Health, Providence, RI, USA, Department of Family Medicine, Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Charles B
authors.initials: CB
authors.lastname: Eaton
authors.affiliation: Department of Epidemiology, Brown University School of Public Health, Providence, RI, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Buka
authors.affiliation: Department of Epidemiology, Brown University School of Public Health, Providence, RI, USA.
authors.forename: Eric B
authors.initials: EB
authors.lastname: Loucks
mesh_terms: D015502:Absorptiometry, Photon; D000273:Adipose Tissue / Q000378:metabolism*; D050154:Adiposity / Q000235:genetics*; D000328:Adult; D015992:Body Mass Index; D019175:DNA Methylation; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009511:New England; D012307:Risk Factors
keywords: Adiposity; DNA methylation; adipose tissue; epigenetics