A study on the genetic etiology and clinical phenotypes of childhood obesity based on whole exome sequencing technology

HUANG Hui; YANG Yu; LIANG Yi-wei

doi:10.19538/j.ek2024120611

Abstract：Objective To explore the genetic etiology and clinical phenotypes of non-syndromic obesity in children and adolescents.Methods We collected the data of 391 non-syndromic obese children aged 7-14 years,who were admitted to the Department of Endocrinology,Genetics and Metabolism of Jiangxi Children's Hospital from January 2020 to June 2022.Whole-exome sequencing was employed to identify potential genetic causes,followed by a detailed analysis of copy number variations(CNVs),obesity-associated target genes,and 79 previously reported candidate genes for obesity.The American College of Medical Genetics and Genomics(ACMG)guidelines were utilized to classify genetic variants and to analyze gene variations and clinical phenotypes.Results The study cohort comprised 391 non-syndromic obese children and adolescents,all of whom exhibited obesity symptoms before the age of 10,with 302 males and 90 females,resulting in a male-to-female ratio of 3.38∶1.Genetic screening outcomes:A total of 32 cases(8.2％)were identified carrying 18 non-syndromic obesity genes,with a male-to-female ratio of 2.2∶1 in the positive group.The majority of these cases were observed in the 9-12-year-old age bracket,with UCP3 and MC4R being the most common genes.Clinical-genetic correlations:Univariate and multivariate logistic regression analyses revealed that there were significant statistical differences in urinary trace proteins,free thyroxine(fT4),serum alanine aminotransferase(ALT),serum glutamyl transpeptidase(GGT),uric acid,blood phosphorus,paternal weight,family history of diabetes,obesity and hypertension,impaired glucose tolerance(IGT),non-high-density lipoprotein cholesterol(non-HDL-C),and complicated metabolic syndrome(P＜0.05).Multivariate Logistics statistical analysis showed that blood phosphorus emerged as an independent risk factor for genetic factors of obesity in children and adolescents(P＜0.05).Conclusion This study has identified UCP3 and MC4R as the most prevalent genes associated with non-syndromic obesity in children and adolescents,suggesting their potential as key genetic markers.Based on univariate analysis,a nomogram prediction model is developed and validated to serve as a clinical tool for risk prediction and to guide the screening of genetically susceptible children.