Oncotarget

Research Papers:

The role of established East Asian obesity-related loci on pediatric leptin levels highlights a neuronal influence on body weight regulation in Chinese children and adolescents: the BCAMS study

Junling Fu, Ge Li, Lujiao Li, Jinhua Yin, Hong Cheng, Lanwen Han, Qian Zhang, Naishi Li, Xinhua Xiao, Struan F.A. Grant, Mingyao Li, Shan Gao, Jie Mi and Ming Li _

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Oncotarget. 2017; 8:93593-93607. https://doi.org/10.18632/oncotarget.20547

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Abstract

Junling Fu1, Ge Li1, Lujiao Li1, Jinhua Yin1, Hong Cheng2, Lanwen Han3, Qian Zhang1, Naishi Li1, Xinhua Xiao1, Struan F.A. Grant4,5,6, Mingyao Li7, Shan Gao3, Jie Mi2 and Ming Li1

1Department of Endocrinology, Key Laboratory of Endocrinology, National Health and Family Planning Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, P.R. China

2Department of Epidemiology, Capital Institute of Paediatrics, Beijing, P.R. China

3Department of Endocrinology, Chaoyang Hospital, Capital Medical University, Beijing, P.R. China

4Division of Endocrinology, The Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

5Division of Human Genetics, The Children’s Hospital of Philadelphia Research Institute, Philadelphia, PA, USA

6Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

7Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA

Correspondence to:

Ming Li, email: liming@pumch.cn

Keywords: obesity, SNP, leptin, adipokine, children

Received: April 02, 2017    Accepted: August 08, 2017    Published: August 24, 2017

ABSTRACT

Genome-wide association studies have identified multiple variants associated with adult obesity, mostly in European-ancestry populations. We aimed to systematically assess the contribution of key loci, which had been previously shown to be associated in East Asian adults, to childhood obesity, related adipokine profiles and metabolic traits in a Chinese pediatric population. Twelve single-nucleotide polymorphisms (SNPs) plus metabolic profiles and levels of five adipokines (leptin, adiponectin, resistin, fibroblast growth factor 21 and retinol binding protein 4) were evaluated in 3,506 Chinese children and adolescents aged 6-18. After correction for multiple comparisons, six of these SNPs were robustly associated with childhood obesity: FTO-rs1558902 (P=5.6×10−5), MC4R-rs2331841 (P=4.4×10−4), GNPDA2-rs16858082 (P = 3.4×10−4), PCSK1-rs261967 (P = 0.001), SEC16B-rs516636 (P = 0.004) and MAP2K5-rs4776970 (P = 0.004), with odds ratios ranging from 1.211 to 1.421; while ITIH4-rs2535633 and BDNF-rs2030323 yielded nominal association with the same trait (P < 0.05). Moreover, the risk alleles of six SNPs displayed significant (P < 0.004) or nominal (P < 0.05) association with leptin levels, namely at in/near PCSK1, MC4R, FTO, MAP2K5, GNPDA2 and BDNF plus their cumulative genetic score yielded stronger association with increased leptin levels (P = 6.2×10−11). Our results reveal that key obesity-associated loci previously reported in Europeans, but also associated with East Asian adults, are also associated with obesity and/or metabolic quantitative traits in Chinese children. These associations coincide with six brain-expressed loci that correlate with leptin levels, thus may point to an important neuronal influence on body weight regulation in the pediatric setting.


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