DNA methylation of the LY86 gene is associated with obesity, insulin resistance, and inflammation

Shaoyong Su, Haidong Zhu, Xiaojing Xu, Xiaoling Wang, Xin Wang, Yanbin Dong, Kakota Gaston Kapuku, Frank Treiber, Bernard Gutin, Gregory A Harshfield, Harold Snieder

Research output: Contribution to journalArticle

22 Citations (Scopus)

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. Method: 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). Conclusion: By focusing on recent GWAS findings in genome-wide methylation profiles, we identified a solid association between LY86 gene DNA methylation and obesity.

Original languageEnglish (US)
Pages (from-to)183-191
Number of pages9
JournalTwin Research and Human Genetics
Volume17
Issue number3
DOIs
StatePublished - Jan 1 2014

Fingerprint

Methylation
Insulin Resistance
Obesity
Lymphocytes
Inflammation
Antigens
Genome-Wide Association Study
DNA
Genes
Genome
Epigenomics
Adiposity
Population
Healthy Volunteers
Cross-Sectional Studies

Keywords

  • DNA methylation
  • GWAS
  • inflammation
  • insulin resistance
  • obesity

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynecology
  • Genetics(clinical)

Cite this

DNA methylation of the LY86 gene is associated with obesity, insulin resistance, and inflammation. / Su, Shaoyong; Zhu, Haidong; Xu, Xiaojing; Wang, Xiaoling; Wang, Xin; Dong, Yanbin; Kapuku, Kakota Gaston; Treiber, Frank; Gutin, Bernard; Harshfield, Gregory A; Snieder, Harold.

In: Twin Research and Human Genetics, Vol. 17, No. 3, 01.01.2014, p. 183-191.

Research output: Contribution to journalArticle

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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. Method: 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). Conclusion: By focusing on recent GWAS findings in genome-wide methylation profiles, we identified a solid association between LY86 gene DNA methylation and obesity.",
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AU - Xu, Xiaojing

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AU - Dong, Yanbin

AU - Kapuku, Kakota Gaston

AU - Treiber, Frank

AU - Gutin, Bernard

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