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

Abstract

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.

A coding variant in SULT1A2 gene: association with obesity and dyslipidemia in southern Chinese adults

“…This case-control study identi ed the genetic association of SULT1A2 rs1059491 variant with obesity in Taizhou adults, and found the G allele over-represented in the normal weight group. However, our previous study indicated that the G allele is a risk factor for obesity in children from northern China [11]. This inconsistency may be due to age and regional differences between the two populations.…”

“…Assuming a dominant genetic model, an allele frequency of 0.06, and overweight and obesity prevalence of 50% in the adults of China, we estimated that an enrollment target of 466 participants (233 per group) would provide the study with greater than 80% statistical power to detect a signi cant odds ratio of 2.3 for risk of overweight and obesity between the different genotype groups at a signi cance level of 0.05 using a two-tailed test. The anticipated effect size for risk of obesity was determined on the basis of previous data obtained from northern Chinese children and adolescents [11].…”

“…Different software predictions show that rs1059491: p.Asn235Thr ( c.704T / G ) is related with gene function ('probably damaging' PolyPhen-2, 'non-neutral' SNAP and 'deleterious' SIFT ). However, our previous ndings suggest rs1059491 was an eQTL that may contribute to obesity by altering the expression of obesity-related gene rather than affecting protein structure [11]. Available transcriptome and GETx data revealed that rs1059491 was located at transcription factor binding sites of PPARγ2 and RXRA [16], which could lead to abnormal lipid metabolism and obesity.…”

“…In addition, exome-wide scan showed SULT1A2 gene is highly expressed in healthy liver and may be involved in the pathogenesis of non-alcoholic fatty liver disease [10]. Furthermore, we have previously demonstrated the coding variant rs1059491 in SULT1A2 was associated with childhood obesity at genome-wide level in Northern China [11].…”

MAP3K Family Review and Correlations with Patient Survival Outcomes in Various Cancer Types

“…Additionally, MAP3K21 is an NIH designated IDG-eligible kinase. Existing reports identify a correlation between MAP3K21 and pediatric obesity, E. coli induced diarrhea, and disease resistance in African chickens [150][151][152].…”