An epigenome-wide study of obesity in African American youth and young adults: novel findings, replication in neutrophils, and relationship with gene expression

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  • Wang, Xiaoling
    • Other Affiliation: Department of Pediatrics, Georgia Prevention Institute, Medical College of Georgia, Augusta University, Augusta, USA
  • Pan, Yue
    • Other Affiliation: Department of Pediatrics, Georgia Prevention Institute, Medical College of Georgia, Augusta University, Augusta, USA
  • Zhu, Haidong
    • Other Affiliation: Department of Pediatrics, Georgia Prevention Institute, Medical College of Georgia, Augusta University, Augusta, USA
  • Hao, Guang
    • Other Affiliation: Department of Pediatrics, Georgia Prevention Institute, Medical College of Georgia, Augusta University, Augusta, USA
  • Huang, Yisong
    • Other Affiliation: Department of Pediatrics, Georgia Prevention Institute, Medical College of Georgia, Augusta University, Augusta, USA
  • Barnes, Vernon
    • Other Affiliation: Department of Pediatrics, Georgia Prevention Institute, Medical College of Georgia, Augusta University, Augusta, USA
  • Shi, Huidong
    • Other Affiliation: Cancer Center, Augusta University, Augusta, USA
  • Snieder, Harold
    • Other Affiliation: Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
  • Pankow, James
    • Other Affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, USA
  • North, Kari
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Grove, Megan
    • Other Affiliation: Human Genetics Center, School of Public Health, University of Texas Health Sciences Center at Houston, Houston, USA
  • Guan, Weihua
    • Other Affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, USA
  • Demerath, Ellen
    • Other Affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, USA
  • Dong, Yanbin
    • Other Affiliation: Department of Pediatrics, Georgia Prevention Institute, Medical College of Georgia, Augusta University, Augusta, USA
  • Su, Shaoyong
    • Other Affiliation: Department of Pediatrics, Georgia Prevention Institute, Medical College of Georgia, Augusta University, Augusta, USA
Abstract
  • Background We conducted an epigenome-wide association study (EWAS) on obesity in healthy youth and young adults and further examined to what extent identified signals influenced gene expression and were independent of cell type composition and obesity-related cardio-metabolic risk factors. Genome-wide DNA methylation data from leukocytes were obtained from 700 African Americans aged 14–36. We also measured genome-wide DNA methylation data from neutrophils as well as genome-wide gene expression data from leukocytes in a subset of samples (n = 188). Results The EWAS identified 76 obesity-related CpG sites in leukocytes with p < 1 × 10−7. In silico replication in the ARIC study of 2097 African Americans aged 47–70 validated 54 CpG sites. Out of the 54 CpG sites, 29 associations with obesity were novel and 37 were replicated in neutrophils. Fifty one CpG sites were associated with at least one cardio-metabolic risk factor; however, the number reduced to 9 after adjustment for obesity. Sixteen CpG sites were associated with expression of 17 genes in cis, of which 5 genes displayed differential expression between obese cases and lean controls. We also replicated 71.5% of obesity-related CpG sites previously reported. Conclusion In this study of youth and young adults, we identified 29 novel CpG sites associated with obesity and replicated the majority of the CpG sites previously identified. We further demonstrated that the majority of the obesity-related CpG sites in leukocytes were not driven by cell composition or obesity-related cardio-metabolic risk factors. We also provided the direct link between DNA methylation-gene expression-obesity for 5 genes.
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  • Article
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  • In Copyright
Rights holder
  • The Author(s).
Journal title
  • Clinical Epigenetics
Journal volume
  • 10
Journal issue
  • 1
Page start
  • 3
Language
  • English
Bibliographic citation
  • Clinical Epigenetics. 2018 Jan 05;10(1):3
Publisher
  • BioMed Central

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