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Obesity (Silver Spring). 2015 Jul;23(7):1493-501. doi: 10.1002/oby.21111.

Epigenome-wide study identifies novel methylation loci associated with body mass index and waist circumference.

Author information

1
Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA.
2
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.
3
Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
4
Framingham Heart Study, Framingham, Massachusetts, USA.
5
Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, USA.
6
Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA.
7
Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.
8
Department of Epidemiology, School of Public Health, Harvard University, Boston, Massachusetts, USA.
9
Department of Biostatistics, School of Public Health, Harvard University, Boston, Massachusetts, USA.
10
Department of Biostatistics, Boston University, Boston, Massachusetts, USA.
11
Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA.
12
Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Texas, USA.
13
HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.
14
Division of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
15
School of Medicine, University of Utah, Salt Lake City, Utah, USA.
16
Division of Statistical Genomics, Department of Genetics, Washington University in St Louis, St Louis, Missouri, USA.
17
Department of Epidemiology, Atherothrombosis and Imaging, Centro Nacional De Investigaciones Cardiovasculares, Madrid, Spain.
18
Instituto Madrileño De Estudios Avanzados Alimentacion, Madrid, Spain.
19
Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA.

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.

PMID:
26110892
PMCID:
PMC4482015
DOI:
10.1002/oby.21111
[Indexed for MEDLINE]
Free PMC Article

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