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Coding Variants Affecting the Expression of Obesity-related Genes for Pediatric Adiposity
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  • Ke Mao,
  • Meixian Zhang,
  • Jinshuai Cao,
  • Xiaoyuan Zhao,
  • Liwang Gao,
  • Liwan Fu,
  • Hong Cheng,
  • Chun Yan,
  • Xiaopeng Xu,
  • Xiaofeng Shi,
  • Zhuoyuan Jiang,
  • Bingqing Wang,
  • Yong-Biao Zhang,
  • Jie Mi
Ke Mao
Beihang University
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Meixian Zhang
Department of Epidemiology, Capital Institute of Paediatrics
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Jinshuai Cao
Beihang University
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Xiaoyuan Zhao
Department of Epidemiology, Capital Institute of Paediatrics
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Liwang Gao
Department of Epidemiology, Capital Institute of Paediatrics
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Liwan Fu
Beijing Children's Hospital, Capital Medical University, National Center for Children's Health
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Hong Cheng
Department of Epidemiology, Capital Institute of Paediatrics
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Chun Yan
Beihang University
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Xiaopeng Xu
Beihang University
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Xiaofeng Shi
Beihang University
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Zhuoyuan Jiang
Beihang University
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Bingqing Wang
Beihang University
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Yong-Biao Zhang
Beihang University
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Jie Mi
Beijing Children's Hospital, Capital Medical University, National Center for Children's Health
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Abstract

Objective Heredity has a remarkable effect on obesity in an obesogenic environment. Despite numerous genetic variants contributing to obesity-related traits, none of them was identified from Chinese children. We aim to identify novel variants and genes associated with childhood obesity in China. Methods We obtain promising single nucleotide variants from 76 obese and 74 normal weight children by whole-exome sequencing, and interrogate their associations with obesity traits in an additional 6,334 children cohort. We then depict the effects of genome-wide significant (P < 5E-8) variants on expression of implicated genes in blood and adipose tissues by transcriptome sequencing. Results We identify two coding variants associated with obesity at genome-wide significance: rs1059491 (P = 2.57E-28) in SULT1A2 and rs189326455 (P = 8.98E-12) in MAP3K21. In addition, rs1058491 is also significantly associated with several obesity traits. Transcriptome sequencing demonstrates that rs1059491 is an eQTL site associated with the expression levels of several obesity-related genes, such as SULT1A2, ATXN2L, and TUFM. Conclusions Our work identifies two coding variants affecting the expression of obesity-related genes based on a large Chinese pediatric adiposity cohort and provide new insights for the pathophysiology of Chinese childhood obesity.