Coding Variants are Relevant to the Expression of Obesity‐Related Genes for Pediatric Adiposity

Objective Heredity has a remarkable effect on obesity in an obesogenic environment. Despite the numerous genetic variants that contribute to obesity‐related traits, none has been identified in Chinese children. This study aimed to identify novel variants associated with childhood obesity in China. M...

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Published in:Obesity (Silver Spring, Md.) Md.), 2021-01, Vol.29 (1), p.194-203
Main Authors: Mao, Ke, Zhang, Meixian, Cao, Jinshuai, Zhao, Xiaoyuan, Gao, Liwang, Fu, Liwan, Cheng, Hong, Yan, Chun, Xu, Xiaopeng, Shi, Xiaofeng, Jiang, Zhuoyuan, Wang, Bingqing, Zhang, Yong‐Biao, Mi, Jie
Format: Article
Language:English
Subjects:
Age
Children & youth
Cholesterol
Deoxyribonucleic acid
Diabetes
DNA
Genomes
Genomics
Obesity
Pathophysiology
Pediatrics
Teenagers
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Summary:Objective Heredity has a remarkable effect on obesity in an obesogenic environment. Despite the numerous genetic variants that contribute to obesity‐related traits, none has been identified in Chinese children. This study aimed to identify novel variants associated with childhood obesity in China. Methods Promising single‐nucleotide variants were obtained using whole‐exome sequencing from 76 children who had obesity and 74 children with normal weight, and their associations with obesity‐related traits in an additional 6,334‐child cohort were investigated. The effects of the genome‐wide significant (P < 5E‐8) variants on the expression of the implicated genes in blood and adipose tissue were then depicted using transcriptome sequencing. Results Two coding variants associated with obesity with genome‐wide significance were identified: rs1059491 (P = 2.57E‐28) in SULT1A2 and rs189326455 (P = 8.98E‐12) in MAP3K21. In addition, rs1059491 was also significantly associated with several obesity traits. Transcriptome sequencing demonstrated that rs1059491 and rs189326455 were expression quantitative trait loci relevant to the expression levels of several obesity‐related genes, such as SULT1A2, ATXN2L, TUFM, and MAP3K21. Conclusions This work identified two coding variants that were significantly associated with pediatric adiposity and were expression quantitative trait loci for obesity‐related genes. This study provides new insights into the pathophysiology of Chinese childhood obesity.
ISSN:1930-7381
1930-739X
DOI:10.1002/oby.23046