Phenotyping obesity using behavioral, psychological, physiological, familial, and genetic data

摘要 肥胖在美国青少年和年轻人中仍然非常普遍， 相对较少的超重或肥胖的年轻人能够减肥并保持减肥，因此 把预防放在首位。尽管有一系列的遗传基因和行为 预测体重变化和肥胖的环境因素已经被确定为前瞻性的 研究表明，它们与体重增加和肥胖的关联程度并不大。此外， 旨在预防儿童和青少年肥胖的众多临床试验取得了成果。 影响不大。在观察性研究中没有观察到大的影响的一个可能的原因是 临床试验表明，所有类型的超重和肥胖通常被归类在一起。一种潜力 忽视肥胖的异质性的后果是缺少或低估了 肥胖的特定亚型。另一种策略是识别亚型并检查亚型- 特定的关联。对肥胖进行更仔细的表型鉴定可能会被用来促进 肥胖症流行病学和治疗领域。需要研究来确定肥胖的范围 表型以及肥胖亚型是否存在生物性别和种族的差异。我们 建议使用食欲行为，心理，行为，人体测量，生理，遗传， 和家庭数据，以个人为中心的方法，从经验上识别肥胖的亚型，并 调查这些亚型是否因生物性别或种族而异。我们将使用从 2379名女孩参与国家生长与健康研究，1421名儿童(48%肥胖，17%肥胖 超重)在尤尼斯·施莱弗·肯尼迪国家医院的生长和肥胖部分进行了研究 儿童健康与人类发展研究所(儿童健康与人类发展研究所)和16,850名成长中的青年 今日研究(14.9%的人肥胖，29%的人超重)。我们将使用潜在类分析来 确定肥胖的亚群，然后检查经验派生的表型是否 预测青春期和青春期体重变化、高血压的发生 年龄在35岁之前，或与肥胖基因座有不同的关联模式。此外，我们还将 检查表型是否因生物性别或种族而不同，以及是否与 青春期和青春期体重变化的表型与儿童发育的关系 35岁以前的高血压，因生物性别或种族而异。我们提议的研究结果可能 对这一领域有重大影响。缩小种族和性别差异的第一步是 检查疾病的表现和病程是否有差异。我们的研究将提供这一点 提供急需的信息，这可能导致量身定做和更有效的预防和治疗。

ABSTRACT Obesity remains highly prevalent among adolescents and young adults in the United States and relatively few youth with overweight or obesity are able to lose weight and maintain the loss, thus making prevention of paramount importance. Although a range of genetic loci and behavioral and environmental factors predictive of weight change and obesity have been identified in prospective studies, their associations with weight gain and obesity have been modest in magnitude. Moreover, the numerous clinical trials aimed at prevention of obesity in children and adolescents have yielded modest effects. One possible reason for the lack of observing large effects in observational studies or clinical trials is that all types of overweight and obesity are often grouped together. One potential consequence of overlooking the heterogeneity in obesity is missing or underestimating risk factors for specific subtypes of obesity. An alternative strategy is to identify subtypes and examine subtype- specific associations. More careful phenotyping of obesity could potentially be used to advance the field of obesity epidemiology and treatment. Research is needed to identify the range of obesity phenotypes and whether there are differences in obesity subtypes by biological sex and race. We propose using appetitive behaviors, psychological, behavioral, anthropometric, physiological, genetic, and familial data, in a person-centered approach to empirically identify subtypes of obesity and to investigate whether the subtypes vary by biological sex or race. We will use data collected from the 2379 girls in National Growth and Health Study, 1421 children (48% with obesity and 17% with overweight) studied in the Section on Growth and Obesity at the Eunice Shriver Kennedy National Institute of Child Health and Human Development (NICHD), and the 16,850 youth in the Growing Up Today Study (14.9% with obesity and 29% with overweight). We will use latent class analysis to identify subgroups of obesity and then examine whether the empirically-derived phenotypes are predictive of weight change in adolescence and young adulthood, the development of hypertension before age 35, or have a differential pattern of association with the obesity loci. In addition, we will examine whether the phenotypes vary by biological sex or race and whether the associations of phenotypes with weight change in adolescence and young adulthood and the development of hypertension before age 35, vary by biological sex or race. The results of our proposed study could have a major impact on the field. The first step towards decreasing disparities by race and sex is to examine if there are differences in presentation and course of a disorder. Our study will provide that much needed information, which could result in tailored and more effective prevention and treatments.