Coding Variants Affecting the Expression of Obesity-related Genes for
Pediatric Adiposity
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.