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Coding Variants are Relevant to the Expression of Obesity-Related Genes for Pediatric Adiposity
Ke Mao1, Meixian Zhang2, Jinshuai Cao1
1Interdisciplinary Innovation Institute of Medicine and Engineering, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
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.
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