多基因风险评分在儿童肥胖干预效果可持续性中的作用

Effect of polygenic risk score in the sustainability of childhood obesity intervention

目的 探索多基因风险评分(PRS)与儿童肥胖干预效果可持续性的关联,为未来开展基于遗传背景、可持续、个性化的儿童肥胖干预提供科学依据。方法 从一项研究儿童干预效果的整群随机对照试验(2018年9月—2021年4月)中,选取北京地区148名基线时处于超重肥胖的儿童作为研究对象,采集唾液进行全基因组测序。构建4个PRS:加权和未加权PRS69,加权和未加权PRS_(67)。分析PRS与干预组别对干预效果可持续性(干预结束到最后一次随访期间肥胖相关指标变化)的交互作用。结果 PRS与干预组别对干预结束后儿童校正体质量指数(BMI)的腰围、校正BMI的腰臀比和收缩压的反弹程度存在交互作用。与对照组相比,干预组儿童加权PRS69每增加一个单位(1个s),校正BMI的腰围(β=0.34,95%CI:0.05~0.63,P=0.020)和校正BMI的腰臀比(β=0.29,95%CI:0.03~0.56,P=0.031)在干预结束后反弹得越多;加权PRS_(67)和未加权PRS_(67)每增加一个单位(1个s),收缩压在干预结束后反弹得越多(β=3.58,95%CI:0.50~6.66,P=0.023;β=3.75,95%CI:0.78~6.71,P=0.014)。结论 超重肥胖儿童PRS越高(携带风险等位基因越多),其在干预结束后的校正BMI的腰围、校正BMI的腰臀比和收缩压越容易反弹。未来应在干预结束后重点关注这些高危儿童的饮食和运动行为,预防和控制发生肥胖反弹。

Objective To explore the relationship between polygenic risk score(PRS)and the sustainability of childhood obesity intervention,in order to provide scientific basis for future sustainable and personalized childhood obesity intervention based on genetic background.Methods A total of 148 children with overweight/obesity at baseline were selected as study subjects from a cluster randomized controlled trial(September 2018 to April 2021)regarding the effect of a childhood obesity intervention in Beijing,China.Saliva was collected to detect the whole genome sequencing.Four PRSs were built:weighted and unweighted PRS69,weighted and unweighted PRS_(67).The interactions between PRS and study arms on the sustainability of intervention effect(the changes in obesity-related indicators between the end of the intervention and the last follow-up)were analyzed.Results There were interactions between PRS and study arms on the rebound degree of waist circumference adjusted for body mass index(BMI),waist-to-hip ratio adjusted for BMI,and systolic blood pressure after the intervention.Compared with the control group,children in the intervention group carried each additional unit(standard deviation)of weighted PRS69,the waist circumference adjusted for BMI rebounded more by 0.34(95%CI:0.05-0.63,P=0.020),and waist-to-hip ratio adjusted for BMI rebounded more by 0.29(95%CI:0.03-0.56,P=0.031)at the last follow-up survey.When children in the intervention group carried each additional unit(standard deviation)of weighted PRS_(67) and unweighted PRS_(67),systolic blood pressure at the last follow-up survey rebounded more by 3.58(95%CI:0.50-6.66,P=0.023)and 3.75(95%CI:0.78-6.71,P=0.014),respectively.Conclusions The higher PRS(the more risk alleles)children with overweight/obesity carried,their waist circumference,waist-to-hip ratio and systolic blood pressure are more likely to rebound after the intervention.Findings from this study suggest that future studies should focus more on these high-risk children after the intervention to prevent and control obesity rebound.