title: Epigenome-wide study identifies novel methylation loci associated with body mass index and waist circumference.
abstract: OBJECTIVE
  To conduct an epigenome-wide analysis of DNA methylation and obesity traits.
  
  
  METHODS
  DNA methylation was quantified in CD4+ T-cells using the Illumina Infinium HumanMethylation450 array in 991 participants of the Genetics of Lipid Lowering Drugs and Diet Network. Methylation at individual cytosine-phosphate-guanine (CpG) sites as a function of body mass index (BMI) and waist circumference (WC), adjusting for age, gender, study site, T-cell purity, smoking, and family structure, was modeled.
  
  
  RESULTS
  Epigenome-wide significant associations between eight CpG sites and BMI and five CpG sites and WC, successfully replicating the top hits in whole blood samples from the Framingham Heart Study (n = 2,377) and the Atherosclerosis Risk in Communities study (n = 2,097), were found. Top findings were in CPT1A (meta-analysis P = 2.7 × 10(-43) for BMI and 9.9 × 10(-23) for WC), PHGDH (meta-analysis P = 2.0 × 10(-15) for BMI and 4.0 × 10(-9) for WC), CD38 (meta-analysis P = 6.3 × 10(-11) for BMI and 1.6 × 10(-12) for WC), and long intergenic non-coding RNA 00263 (meta-analysis P = 2.2 × 10(-16) for BMI and 8.9 × 10(-14) for WC), regions with biologically plausible relationships to adiposity.
  
  
  CONCLUSIONS
  This large-scale epigenome-wide study discovered and replicated robust associations between DNA methylation at CpG loci and obesity indices, laying the groundwork for future diagnostic and/or therapeutic applications.
authors.affiliation: Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Stella
authors.initials: S
authors.lastname: Aslibekyan
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Ellen W
authors.initials: EW
authors.lastname: Demerath
authors.affiliation: Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.|Framingham Heart Study, Framingham, Massachusetts, USA.|Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Mendelson
authors.affiliation: Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Degui
authors.initials: D
authors.lastname: Zhi
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Weihua
authors.initials: W
authors.lastname: Guan
authors.affiliation: Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.|Framingham Heart Study, Framingham, Massachusetts, USA.|Department of Epidemiology, School of Public Health, Harvard University, Boston, Massachusetts, USA.|Department of Biostatistics, School of Public Health, Harvard University, Boston, Massachusetts, USA.
authors.forename: Liming
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Sha
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: James S
authors.initials: JS
authors.lastname: Pankow
authors.affiliation: Framingham Heart Study, Framingham, Massachusetts, USA.|Department of Biostatistics, Boston University, Boston, Massachusetts, USA.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Marguerite R
authors.initials: MR
authors.lastname: Irvin
authors.affiliation: Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA.|Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Texas, USA.
authors.forename: Myriam
authors.initials: M
authors.lastname: Fornage
authors.affiliation: Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Bertha
authors.initials: B
authors.lastname: Hidalgo
authors.affiliation: Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Texas, USA.
authors.forename: Li-An
authors.initials: LA
authors.lastname: Lin
authors.affiliation: HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.
authors.forename: Krista Stanton
authors.initials: KS
authors.lastname: Thibeault
authors.affiliation: Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Texas, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Bressler
authors.affiliation: Division of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Tsai
authors.affiliation: Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Texas, USA.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Grove
authors.affiliation: School of Medicine, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Hopkins
authors.affiliation: Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA.|Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Texas, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.affiliation: Division of Statistical Genomics, Department of Genetics, Washington University in St Louis, St Louis, Missouri, USA.
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Borecki
authors.affiliation: Department of Epidemiology, Atherothrombosis and Imaging, Centro Nacional De Investigaciones Cardiovasculares, Madrid, Spain.|Instituto Madrileño De Estudios Avanzados Alimentacion, Madrid, Spain.|Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
authors.affiliation: Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.|Framingham Heart Study, Framingham, Massachusetts, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.affiliation: Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Hemant K
authors.initials: HK
authors.lastname: Tiwari
authors.affiliation: HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.
authors.forename: Devin M
authors.initials: DM
authors.lastname: Absher
authors.affiliation: Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
mesh_terms: D015992:Body Mass Index; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D057890:Epigenomics / Q000379:methods*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D010641:Phenotype; D055105:Waist Circumference / Q000235:genetics*
chemical_list: C577474:CPT1A protein, human; D002334:Carnitine O-Palmitoyltransferase