TY - JOUR
T1 - DNA methylation of the LY86 gene is associated with obesity, insulin resistance, and inflammation
AU - Su, Shaoyong
AU - Zhu, Haidong
AU - Xu, Xiaojing
AU - Wang, Xiaoling
AU - Wang, Xin
AU - Dong, Yanbin
AU - Kapuku, Kakota Gaston
AU - Treiber, Frank
AU - Gutin, Bernard
AU - Harshfield, Gregory A
AU - Snieder, Harold
PY - 2014/6
Y1 - 2014/6
N2 - 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.
AB - 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.
KW - DNA methylation
KW - GWAS
KW - inflammation
KW - insulin resistance
KW - obesity
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U2 - 10.1017/thg.2014.22
DO - 10.1017/thg.2014.22
M3 - Article
C2 - 24735745
AN - SCOPUS:84901694758
SN - 1832-4274
VL - 17
SP - 183
EP - 191
JO - Twin Research and Human Genetics
JF - Twin Research and Human Genetics
IS - 3
ER -