Oncotarget

Research Papers:

MeQTL analysis of childhood obesity links epigenetics with a risk SNP rs17782313 near MC4R from meta-analysis

Yuping Tang, Bo Jin, Lingling Zhou and Weifeng Lu _

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Oncotarget. 2017; 8:2800-2806. https://doi.org/10.18632/oncotarget.13742

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Abstract

Yuping Tang1,*, Bo Jin2,*, Lingling Zhou1,*, Weifeng Lu3

1Department of Orthopaedic, Children’s Hospital of Nanjing Medical University, Nanjing, China

2Department of Neurology, Children’s Hospital of Nanjing Medical University, Nanjing, China

3Surgical Intensive Care Unite, Children’s Hospital of Nanjing Medical University, Nanjing, China

*These authors contributed equally to this work

Correspondence to:

Weifeng Lu, email: [email protected]

Keywords: rs17782313, MC4R, meQTL, eQTL, childhood obesitys

Received: September 22, 2016     Accepted: November 23, 2016     Published: December 01, 2016

ABSTRACT

Earlier GWAS has identified that rs17782313 near MC4R was associated with obesity. However, subsequent studies showed conflicting results, especially among childhood. Besides, the mechanisms underlying the association between rs17782313 and childhood obesity remain largely unexplored, and genetic and epigenetic may interact and together affect the development of childhood obesity. We conducted a comprehensive meta-analysis to assess the association between rs17782313 and childhood obesity. MeQTL and eQTL analysis was applied to explore the effect of rs17782313 on DNA methylation and MC4R expression. We found that rs17782313 near MC4R was associated with increased childhood obesity risk and BMI z-score in several inheritable models (P < 0.05). Additionally, the similar trend was observed among subgroups of Asians, Caucasian. Furthermore, meQTL and eQTL analysis indicated that individuals carrying rs17782313 TT genotype were significantly associated with increased methylation level of cg10097150 located in MC4R promoter and decreased expression of MC4R than those with CT/CC genotype (P = 1.7 × 10−4 and P = 1.9 × 10−3 respectively). Our results strongly confirmed that rs17782313 was associated with increased risk of childhood obesity. Furthermore, rs17782313 T allele was correlated with promoter hypermethylation and decreased expression of MC4R, thus involved in the development of childhood obesity.


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