Legends
Figure 1 . The process diagram for investigating genetic
basis of obesity in Chinese children . At discovery stage, whole-exome
sequencing identified promising candidates. At validation and
transcriptome stage, two coding variants that are significant associated
with obesity might act through altering gene expression.
Figure 2 . The genomic context of the genome-wide
significant SNVs associated with childhood obesity in Chinese . Both
rs1059491 (A) and rs189326455 (B) reside in conserved promoter region ofSULT1A2 (NC_000016.10) and MAP3K21 (NC_000001.11),
respectively. (C) The T allele (ancestral) and G allele (derived) show
different binding ability to transcription factors. Red lines indicate
the locus of rs1059491. Orange blocks indicate the possible binding site
for transcription factors.
Figure 3 . The expression change of genes affected by
rs1059491 . (A) Gene expression differences in blood and adipose tissues
among different genotypes (TT, TG, and GG) of rs1059491. Violin plots
show the expression level of obesity-related genes from GTEx database
and box plots show that of genes from our transcriptome data. (B)
Transcriptome data show that rs1059491 results in significant
differences in obesity-related genes between cases and controls in both
blood and adipose tissues.
Figure 4 . A scheme illustrates the potential
implication of rs1059491 and rs189326455 in obesity .
Supplementary Figure 1. The prediction of secondary structure
changes of SULT1A2 and MAP3K21 caused by mutant allele of rs1059491 and
rs189326455, respectively .
Supplementary Figure 2 . The allele frequency of
rs1059491 in different populations across the world . ACB, African
Caribbean in Barbados. ASW, Americans of African Ancestry in SW USA.
CHB, Han Chinese in Beijing, China. CHS, Southern Han Chinese. CLM,
Colombians from Medellin, Columbia. FIN, Finish in Finland. GBR, British
in England and Scotland. ITU, Indian Telugu from the UK. JPT, Japanese
in Tokyo, Japan. KHV, Kinh in HO Chi Minh City, Vietnam. PEL, Peruvians
from Lima, Peru. PUR, Puerto Ricans from Puerto Rico.