The first genome-wide association study on pediatric obesity in Taiwan

BACKGROUND: The global prevalence of pediatric obesity has risen sharply, increasing from 0.7% to 5.6% in girls and from 0.9% to 7.8% in boys between 1975 and 2016. Genetic factors contribute an estimated 50-80% to obesity risk. In 2007, FTO was identified as the first obesity-associated gene through a genome-wide association study (GWAS), but research in Asian pediatric populations remains limited. This study investigated the genetic architecture of pediatric obesity in Taiwanese children. METHODS: Data were obtained from the China Medical University Hospital Biobank. Obese cases were defined as BMI above 95th percentile for age and sex; controls had BMI between the 3rd and 50th percentiles. GWAS was performed on 5854 cases and 12,343 controls aged 2-17 years using the TPMv1 customized single nucleotide polymorphism (SNP) array. Polygenic risk scores (PRS) were constructed with PRSice2. Phenome-wide association studies (PheWAS) evaluated PRS-disease associations, and network analyses were conducted via Ingenuity Pathway Analysis. (IPA). RESULTS: , with leading SNPs rs79500119 (ASB3, chromosome 2) and rs74617772 (near FTO, chromosome 16). Obesity cases had significantly higher PRS (P < 0.05). PheWAS linked obesity PRS to type 2 diabetes, hypertension, respiratory infections, liver disease, and precocious puberty. Network analysis highlighted the insulin-AKT pathway as potentially central to pathogenesis. CONCLUSIONS: This first GWAS of pediatric obesity in Taiwan revealed novel, population-specific genetic associations. The PRS offers potential for metabolic risk stratification, and the insulin-AKT pathway represents a relevant biological framework for further investigation of pediatric obesity pathogenesis.