Table_1_Genetic associations with neural reward responsivity to food cues in children.docx

ObjectiveTo test associations of candidate obesity-related single nucleotide polymorphisms (SNPs) and obesity polygenic risk scores (PRS) with neural reward reactivity to food cues.
MethodsAfter consuming a pre-load meal, 9–12-year-old children completed a functional magnetic resonance imaging (fMRI) paradigm with exposure to food and non-food commercials. Genetic exposures included FTO rs9939609, MC4R rs571312, and a pediatric-specific obesity PRS. A targeted region-of-interest (ROI) analysis for 7 bilateral reward regions and a whole-brain analysis were conducted. Independent associations between each genetic factor and reward responsivity to food cues in each ROI were evaluated using linear models.
ResultsAnalyses included 151 children (M = 10.9 years). Each FTO rs9939609 obesity risk allele was related to a higher food-cue-related response in the right lateral hypothalamus after controlling for covariates including the current BMI Z-score (p < 0.01), however, the association did not remain significant after applying the multiple testing correction. MC4R rs571312 and the PRS were not related to heightened food-cue-related reward responsivity in any examined regions. The whole-brain analysis did not identify additional regions of food-cue-related response related to the examined genetic factors.
ConclusionChildren genetically at risk for obesity, as indicated by the FTO genotype, may be predisposed to higher food-cue-related reward responsivity in the lateral hypothalamus in the sated state, which, in turn, could contribute to overconsumption.
Clinical trial registrationhttps://clinicaltrials.gov/study/NCT03766191, identifier NCT03766191.

## 研究目的
检验候选肥胖相关单核苷酸多态性（Single Nucleotide Polymorphisms，SNPs）与肥胖多基因风险评分（Polygenic Risk Scores，PRS）对食物线索的神经奖赏反应性的关联。

## 研究方法
9~12岁儿童在进食预负荷餐后，完成了暴露于食物与非食物广告的功能磁共振成像（Functional Magnetic Resonance Imaging，fMRI）任务。本研究的遗传检测指标包括FTO rs9939609、MC4R rs571312以及儿童特异性肥胖多基因风险评分。针对7个双侧奖赏脑区，本研究开展了目标感兴趣区（Region of Interest，ROI）分析，并同时进行全脑分析。采用线性模型评估各遗传因素与各感兴趣区内食物线索奖赏反应性之间的独立关联。

## 研究结果
本分析共纳入151名儿童（平均年龄为10.9岁）。在控制包括当前身体质量指数Z评分（Body Mass Index Z-score，BMI Z评分）在内的协变量后，每一个FTO rs9939609肥胖风险等位基因均与右侧下丘脑外侧区域更高的食物线索相关反应显著相关（p<0.01），但经多重检验校正后，该关联不再具有统计学显著性。MC4R rs571312与肥胖多基因风险评分在所有被检测脑区中均未与增强的食物线索奖赏反应性存在关联。全脑分析未发现与所检测遗传因素相关的额外食物线索反应脑区。

## 研究结论
以FTO基因型为代表的肥胖遗传易感儿童，在饱腹状态下下丘脑外侧区域对食物线索的奖赏反应性可能更高，这或可促成过量进食。

## 临床试验注册
临床试验注册号为NCT03766191，注册链接：https://clinicaltrials.gov/study/NCT03766191。