Impact Of FTO And IRX3 Genetic Variations On Obesity In Primary And Middle School Students In Guangzhou

ObjectiveThis study aimed to identify the environmental factors of obesity among primary and middle school students in Guangzhou,China;to estimate the effect of genetic variations in FTO and IRX3 on obesity in children and adolescents;and to explore the interactions between genes and environmental factors.MethodsBase on the regular medical examinations for elementary and middle school students in Guangzhou,two case-control studies were conducted to analyze the impact of FTO and IRX3 genetic variants and environmental factors on childhood and adolescent obesity.Overweight/obesity and abdominal obesity were screened from 3 grades(grade 2 of primary school,grade 1 of junior and senior high school)students in 39 primary and middle schools;Questionnarie was used to collect the information on general demographic characteristics,eating habits,exercise and lifestyle.Bioinformatics databases,genetic variation prediction tools,and literature were used comprehensively to selected potential functional obesity-related genetic variants;Taq Man real-time PCR was used to performe genotyping.Hardy-Weinberg equilibrium was tested by χ2 test.Unconditional Logistic regression was used to estimate the effect of each environmental factors and genetic variation on obesity;Sequence association tests(SKAT)and SKAT-O were used to explore the combined effect of low-frequency variations;Genetic risk score(GRS)was used to analysis the cumulative effect of risk alleles;Logistic regression models and nonlinear mixed effect models were used to explor gene–environment multiplicative interaction and additive interaction respectively.Data analyses were performed using SAS 9.4 and R 2.3.5.Results(1)A total of 2059 overweight/obesity cases and 2727 controls were included.Environmental factor analysis showed weekday screen time ≥2h/day(OR=1.29,95%CI=1.10~1.50),good appetite(OR=1.48,95%CI= 1.32~1.66),sugar-sweetened beverages ≥500ml(OR=1.19,95%CI=1.05~1.36)positively associated with overweight/obesity;sleep time ≥8h/day(OR=0.76,95%CI= 0.66~0.87)and meal speed ≥10min(OR=0.74,95%CI=0.62~0.89)negatively associated with overweight/obesity.FTOrs16952522,rs9939609 increased the risk of overweight/obesity significantly.Under the additive model,the risk of overweight/obesity increased by approximately 33% for each additional risk allele in rs16952522 or rs9939609 after adjusting gender,grade and other factors.Genetic risk score analysis showed that the risk of overweight/obesity was significantly increased in those with 1,2 and ≥3 scores compared with 0 scores(OR=1.33~1.62,P<0.05).We did not find the interaction between genetic variants and environmental factors for overweight and obesity.(2)There were 1266 abdominal obesity cases and 1381 controls.Weekday screen time ≥2h/day(OR=1.38,95%CI=1.11~1.71),good appetite(OR=1.68,95%CI=1.42~1.98),and sugar-sweetened beverages ≥500ml/ week(OR=1.27,95%CI=1.06~1.53)positively associated with abdominal obesity;moderate-to-vigorous exercise ≥60min/day(OR=0.78,95%CI= 1.61~0.99)negatively associated with abdominal obesity.After adjusting gender,grade,and other factors,the risk of abdominal obesity increased 1.39 times(OR=1.39,95%CI=1.15~1.67)and 1.34 times(OR=1.34,95%CI=1.14~1.57)for each additional risk allele in FTOrs16952522 and rs9939609 under the additive model.Compared with no risk allele carriers,the risk odds for abdominal obesity were 1.35(1.09~1.67)and 2.02(1.13~3.61)for those with 2 and ≥3 genetic risk scores,respectively.Genetic risk scores had additive interactions with appetite for abdominal obesity(Padd,Padd-FDR <0.05).Conclusions Long screens time,good appetite,and excessive consumption of sugar-sweetened beverages are risk factors for overweight/obesity and abdominal obesity among primary and middle school students in Guangzhou;adequate sleep and slow meal speed are protective factors for overweight/obesity;moderate-to-vigorous exercise is protective factor for abdominal obesity.FTOrs16952522 and rs9939609 associate with childhood and adolescent overweight/obesity and abdominal obesity.The interaction between these variants and appetite can increase the risk of abdominal obesity.