title: DNA methylation of the LY86 gene is associated with obesity, insulin resistance, and inflammation.
abstract: BACKGROUND
  Previous genome-wide association studies (GWAS) have identified a large number of genetic variants for obesity and its related traits, representing a group of potential key genes in the etiology of obesity. Emerging evidence suggests that epigenetics may play an important role in obesity. It has not been explored whether the GWAS-identified loci contribute to obesity through epigenetics (e.g., DNA (deoxyribonucleic acid) methylation) in addition to genetics.
  
  
  METHODS
  A multi-stage cross-sectional study was designed. We did a literature search and identified 117 genes discovered by GWAS for obesity and its related traits. Then we analyzed whether the methylation levels of these genes were also associated with obesity in two genome-wide methylation panels. We examined an initial panel of seven adolescent obese cases and seven age-matched lean controls, followed by a second panel of 48 adolescent obese cases and 48 age- and gender-matched lean controls. The validated CpG sites were further replicated in two independent replication panels of youth (46 vs. 46 and 230 cases vs. 413 controls, respectively) and a general population of youth, including 703 healthy subjects.
  
  
  RESULTS
  One CpG site in the lymphocyte antigen 86 (LY86) gene, which showed higher methylation in the obese in both the initial (p = .009) and second genome-wide DNA methylation panel (p = .008), was further validated in both replication panels (meta p = .00016). Moreover, in the general population of youth, the methylation levels of this region were significantly correlated with adiposity indices (p ≤ .02), insulin resistance (p = .001), and inflammatory markers (p < .001).
  
  
  CONCLUSIONS
  By focusing on recent GWAS findings in genome-wide methylation profiles, we identified a solid association between LY86 gene DNA methylation and obesity.
authors.affiliation: Georgia Prevention Center,Georgia Regents University,Augusta,GA,USA.
authors.forename: Shaoyong
authors.initials: S
authors.lastname: Su
authors.affiliation: Georgia Prevention Center,Georgia Regents University,Augusta,GA,USA.
authors.forename: Haidong
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Georgia Prevention Center,Georgia Regents University,Augusta,GA,USA.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Xu
authors.affiliation: Georgia Prevention Center,Georgia Regents University,Augusta,GA,USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Georgia Prevention Center,Georgia Regents University,Augusta,GA,USA.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Georgia Prevention Center,Georgia Regents University,Augusta,GA,USA.
authors.forename: Gaston
authors.initials: G
authors.lastname: Kapuku
authors.affiliation: Technology Applications Center for Healthful Lifestyles,Colleges of Nursing and Medicine,Medical University of South Carolina,Charleston,SC,USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Treiber
authors.affiliation: Georgia Prevention Center,Georgia Regents University,Augusta,GA,USA.
authors.forename: Bernard
authors.initials: B
authors.lastname: Gutin
authors.affiliation: Georgia Prevention Center,Georgia Regents University,Augusta,GA,USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Harshfield
authors.affiliation: Unit of Genetic Epidemiology and Bioinformatics,Department of Epidemiology,University Medical Center Groningen,University of Groningen,Groningen,the Netherlands.
authors.forename: Harold
authors.initials: H
authors.lastname: Snieder
authors.affiliation: Georgia Prevention Center,Georgia Regents University,Augusta,GA,USA.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000954:Antigens, Surface / Q000235:genetics*; D015415:Biomarkers / Q000032:analysis*; D016022:Case-Control Studies; D018899:CpG Islands / Q000235:genetics; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D009765:Obesity / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
chemical_list: D000954:Antigens, Surface; D015415:Biomarkers; C115213:LY86 protein, human
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