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 及 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.