A14343 Whole-Exome Sequencing Identifies a coding variant in SULT1A2 Gene Associated with Obesity in Chinese Children

Abstract

Objectives: Despite numerous genetic variants associated with obesity-related traits have been identified, much of the obesity heritability remains unexplained. We aimed to identify novel coding variants and genes associated with childhood obesity in China. Methods: The study comprised three stages. We conducted deep-depth (50 × ) whole exome sequencing in 18 severely obese and 15 lean children. After several filtering steps, we retained promising single nucleotide variants (SNVs) nominal association (P ≤ 0.05) with obesity, dyslipidemia or impaired plasma glucose for validation in 2,403 obese and 3,778 non-overweight children. Variants showing potential associations were confirmed by Sanger sequencing. Results: Exome sequencing identified 43,264 functional SNVs. We identified two coding variants were associated with common or central obesity at exome-wide significance: rs1059491 in the SULT1A2 gene for common obesity (P = 2.18 × 10–24, odds ratio = 2.16) and rs768847893 in the MXRA5 gene for central obesity (P = 2.57 × 10–8, odds ratio = 2.96, females only). Conclusion: Our findings demonstrate that rs1059491 is strongly associated with common obesity in Chinese children. Additionally, rs768847893 is associated with central obesity in female. Our results provide evidence of the existence of coding variants associated with obesity and have important implications for the pathophysiology of obesity.