Desautels Faculty of Management, McGill Center for the Convergence of Health and Economics, McGill University, Montreal, QC, Canada.
Postgraduate Program in Pediatrics, Universidade Federal de Ciencias da Saude de Porto Alegre, Porto Alegre, RS, Brasil.
PLoS One. 2020 Jun 26;15(6):e0234601. doi: 10.1371/journal.pone.0234601. eCollection 2020.
Body weight is substantially determined by eating behaviors, which are themselves driven by biological factors interacting with the environment. Previous studies in young children suggest that genetic influences on dopamine function may confer differential susceptibility to the environment in such a way that increases behavioral obesity risk in a lower socioeconomic status (SES) environment but decreases it in a higher SES environment. We aimed to test if this pattern of effect could also be observed in adolescence, another critical period for development in brain and behavior, using a novel measure of predicted expression of the dopamine receptor 4 (DRD4) gene in prefrontal cortex. In a sample of 76 adolescents (37 boys and 39 girls from Baltimore, Maryland/US, aged 14-18y), we estimated individual levels of DRD4 gene expression (PredDRD4) in prefrontal cortex from individual genomic data using PrediXcan, and tested interactions with a composite SES score derived from their annual household income, maternal education, food insecurity, perceived resource availability, and receipt of public assistance. Primary outcomes were snack intake during a multi-item ad libitum meal test, and food-related impulsivity assessed using a food-adapted go/no-go task. A linear regression model adjusted for sex, BMI z-score, and genetic ethnicity demonstrated a PredDRD4 by composite SES score interaction for snack intake (p = 0.009), such that adolescents who had lower PredDRD4 levels exhibited greater snack intake in the lower SES group, but lesser snack intake in the higher SES group. Exploratory analysis revealed a similar pattern for scores on the Perceived Stress Scale (p = 0.001) such that the low PredDRD4 group reported higher stress in the lower SES group, but less stress in the higher SES group, suggesting that PredDRD4 may act in part by affecting perceptions of the environment. These results are consistent with a differential susceptibility model in which genes influencing environmental responsiveness interact with environments varying in obesogenicity to confer behavioral obesity risk in a less favorable environment, but behavioral obesity protection in a favorable one.
体重主要由饮食行为决定，而饮食行为本身又受到生物因素与环境的相互作用的影响。先前在幼儿中的研究表明，多巴胺功能的遗传影响可能以这样一种方式赋予对环境的不同易感性，即在社会经济地位（SES）较低的环境中增加行为肥胖风险，但在 SES 较高的环境中降低风险。我们旨在测试这种影响模式是否也可以在青春期观察到，青春期是大脑和行为发育的另一个关键时期，使用前额叶皮层中多巴胺受体 4（DRD4）基因的预测表达的新型测量方法。在马里兰州巴尔的摩的 76 名青少年（37 名男孩和 39 名女孩，年龄 14-18 岁）样本中，我们使用 PrediXcan 根据个体基因组数据估计前额叶皮层中 DRD4 基因的个体表达水平（PredDRD4），并测试与复合 SES 评分的相互作用，该评分源自他们的年度家庭收入、母亲教育程度、食物不安全、感知资源可用性和获得公共援助。主要结果是在多项随意餐测试中摄入零食，以及使用食物适应的 Go/No-Go 任务评估与食物相关的冲动性。调整性别、BMI z 评分和遗传种族的线性回归模型表明，PredDRD4 与复合 SES 评分之间存在相互作用，即 PredDRD4 水平较低的青少年在 SES 较低的组中表现出更大的零食摄入量，但在 SES 较高的组中则更少。探索性分析显示，感知压力量表的评分也存在类似模式（p = 0.001），即低 PredDRD4 组在 SES 较低的组中报告压力更高，但在 SES 较高的组中压力较小，表明 PredDRD4 可能部分通过影响对环境的感知而起作用。这些结果与差异易感性模型一致，即影响环境反应性的基因与肥胖环境不同的环境相互作用，在不利环境中赋予行为肥胖风险，但在有利环境中赋予行为肥胖保护。
