University College London, UK.
King's College London, UK.
JAMA Pediatr. 2014 Apr;168(4):338-344. doi: 10.1001/jamapediatrics.2013.4944.
A better understanding of the cause of obesity is a clinical priority. Obesity is highly heritable, and specific genes are being identified. Discovering the mechanisms through which obesity-related genes influence weight would help pinpoint novel targets for intervention. One potential mechanism is satiety responsiveness. Lack of satiety characterizes many monogenic obesity disorders, and lower satiety responsiveness is linked with weight gain in population samples.
To test the hypothesis that satiety responsiveness is an intermediate behavioral phenotype associated with genetic predisposition to obesity in children.
DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional observational study of a population-based cohort of twins born January 1, 1994, to December 31, 1996 (Twins Early Development Study). Participants included 2258 unrelated children (53.3% female; mean [SD] age, 9.9 [0.8] years), one randomly selected from each twin pair.
Genetic predisposition to obesity. We created a polygenic risk score (PRS) comprising 28 common obesity-related single-nucleotide polymorphisms identified in a meta-analysis of obesity-related genome-wide association studies.
Satiety responsiveness was indexed with a standard psychometric scale (Child Eating Behavior Questionnaire). Using 1990 United Kingdom reference data, body mass index SD scores and waist SD scores were calculated from parent-reported anthropometric data for each child. Information on satiety responsiveness, anthropometrics, and genotype was available for 2258 children. We examined associations among the PRS, adiposity, and satiety responsiveness.
The PRS was negatively related to satiety responsiveness (β coefficient, -0.060; 95% CI, -0.019 to -0.101) and positively related to adiposity (β coefficient, 0.177; 95% CI, 0.136-0.218 for body mass index SD scores and β coefficient, 0.167; 95% CI, 0.126-0.208 for waist SD scores). More children in the top 25% of the PRS were overweight than in the lowest 25% (18.5% vs 7.2%; odds ratio, 2.90; 95% CI, 1.98-4.25). Associations between the PRS and adiposity were significantly mediated by satiety responsiveness (P = .006 for body mass index SD scores and P = .005 for waist SD scores).
These results support the hypothesis that low satiety responsiveness is one of the mechanisms through which genetic predisposition leads to weight gain in an environment rich with food. Strategies to enhance satiety responsiveness could help prevent weight gain in genetically at-risk children.
更好地了解肥胖的原因是临床优先事项。肥胖具有高度遗传性，并且正在确定特定的基因。发现肥胖相关基因影响体重的机制将有助于确定干预的新靶点。一种潜在的机制是饱腹感反应。许多单基因肥胖症都缺乏饱腹感，而在人群样本中，饱腹感反应较低与体重增加有关。
检验饱腹感反应是与儿童肥胖遗传易感性相关的中间行为表型的假设。
设计、地点和参与者：这是一项基于人群的双胞胎队列的横断面观察性研究，双胞胎于 1994 年 1 月 1 日至 1996 年 12 月 31 日出生（双胞胎早期发育研究）。参与者包括 2258 名无血缘关系的儿童（53.3%为女性；平均[标准差]年龄为 9.9[0.8]岁），每对双胞胎中随机选择一名。
肥胖的遗传易感性。我们创建了一个多基因风险评分（PRS），其中包括肥胖相关全基因组关联研究荟萃分析中确定的 28 个常见肥胖相关单核苷酸多态性。
饱腹感反应由标准心理计量表（儿童饮食行为问卷）来衡量。使用 1990 年英国参考数据，根据父母报告的每个儿童的人体测量数据计算体重指数 SD 分数和腰围 SD 分数。2258 名儿童的饱腹感反应、人体测量和基因型信息可用。我们检查了 PRS、肥胖和饱腹感反应之间的关联。
PRS 与饱腹感反应呈负相关（β系数，-0.060；95%置信区间，-0.019 至 -0.101），与肥胖呈正相关（体重指数 SD 评分的β系数，0.177；95%置信区间，0.136-0.218；腰围 SD 评分的β系数，0.167；95%置信区间，0.126-0.208）。PRS 处于前 25%的儿童超重的比例高于处于最低 25%的儿童（18.5%比 7.2%；优势比，2.90；95%置信区间，1.98-4.25）。PRS 与肥胖之间的关联通过饱腹感反应显著中介（体重指数 SD 评分 P = .006，腰围 SD 评分 P = .005）。
这些结果支持低饱腹感反应是遗传易感性导致环境中富含食物时体重增加的机制之一的假设。增强饱腹感反应的策略可能有助于预防遗传风险儿童的体重增加。
