A Study On The Relationship Between Genetic Risk Score And Risk Of Obesity Among Children In Xinjiang

Objective: To study the association between overweight/obesity prevalence and copy number variations?CNVs?among Han,Uyghur,and Kazak children in Xinjiang,China;The ability of genetic risk score?GRS?to reflect genetic joint effects to improve risk assessment of overweight/obesity based on CNV calculations was analyzed.Methods: This study for the National Natural Science Foundation of China?81260440?follow-up survey and laboratory testing part.Stratified cluster random sampling was conducted to select 3⁹ years old childre n?n=5992?in the early stage of the study in four areas of Xinjiang in 2014.A s the research site,taking kindergartens of Ili,Altay and Karamay in Xinjiang,3 to 7 years old children were selected by stratified cluster sampling method and measured the children`s height,weight and collected the oral mucosal exfoliated cells.AccuCopy? multiplex gene copy number method was used to detect the gene copy number variation of APOBR ?ATP2A1?ATXN2L?CHRNA4?COMT?EDN3?EGF?ELOVL6?ETNPPL?FTO?GNAS?GPRIN2?GSTT1?HADH?HES1?IL27?IRX3?ITGAD?ITGAM?MC4R?MIF?OR4P4?OR4S2?PCK1?PRIM2?SH2B1?SYT15 ? TUFM.SPSS 21 software description Uygur Han and Kazakh children CNV distribution and compared;To investigate the relationship between children's overweight / obesity and the CNV of the candidate sites.According to the detection of CNV and the questionnaire,univariate and multivariate analysis were performed on the related factors of overweight / obesity in children.The GRS,ROC and AUC was calculated using SPSS21.0 Binary Logistic,ROC Curve and non-parametric method.NRI and IDI was calculated were using R software.Result:603 children have been surveyed,including 307 men and 296 women;Among them Han was 261,Uyghur was194 and Kazakh was 148,corresponding overweight/obesity rate was 28.3%,10.3% and 31.1%,respectively,this difference had statistically meaning.There were significant differences in the CNV of APOBR,ATP2A1,ATXN2 L,CHR NA4,ELOVL6,FTO₁,GNAS₂,GSTT1,HADH,HES1₁,HES1₂,IL27,IRX3₂,MC4R₂,OR4P4,OR4S2₁,OR4S2₂,PCK1,PRIM2₂ in the three ethnic groups?P<0.05?.There were significant differences in the CNV of OR4P4 and OR4S2₁ in Uygur normal children and overweight / obese children?P<0.05?.The normal body weight and overweight/obesity there were significant differences in gene CNV between IRX3₁ and MC4R₂ in children?P<0.05?.There was a significant difference in CNV of ATXN2 L locus between normal weight and overweight / obese boys?P<0.05?.Single factor and analysis sho wed that children's nationality?OR=6.341,95%CI:1.973²0.380?and?OR=3.349,95%CI:1.092¹0.276?,only child?OR=0.404,95%CI:0.240⁰.679?high family in come?OR=7.76,95%CI:1.816³2.347?,mode of delivery?OR=1.780,95%CI:1.091².903?,CNV exception at IRX3₁ site?OR=2.251,95%1.092⁴.639?were influe nce factors of overweight/obesity.The inclusion of GRS in five traditional overweight / obesity risk factors,including ethnicity,only child,household income,mode of delivery at birth,and CNV abnormalities at IRX3₁ significantly improved the reclassification of the risk of overweight / obesity with NRI and IDI Were 3.85% and 0.024,respectively,all of which were statistically signific ant,but the inclusion of GRS did not significantly increase the AUC,only increased from 0.823 to 0.835?P>0.05?Conclusion: IRX3₁ CNV abnormalities are risk factors for overweight / obesity in children,suggesting that IRX3 as overweight / obesity-related susceptibility genes deserve further study.Children's ethnicity,whether they are singletons,family income,mode of delivery at birth,and CNV abnormalities at IRX3₁ are the most common causes of overweight / obesity in children.The inclusion of GRS in traditional overweight / obesity risk prediction models can significantly improve the reclassification of overweight / obesity risk,but GRS did not significantly improve AUC.