GENETIC EPIDEMIOLOGY OF AGING AND BODY COMPOSITION

对老龄化进行现代遗传流行病学研究带来了巨大的逻辑和分析挑战。关键的逻辑挑战是从中年起获得足够的家族性数据；关键的分析挑战是必须从衰老过程中获得适合分析的具有生物意义的表型。在成年后，男性和女性的身体成分都会发生显著的变化。这些变化会影响骨骼和肌肉的数量，以及脂肪的数量和分布。身体成分的这些变化增加了患骨质疏松症、骨质疏松症和心脏病等复杂疾病的风险。这项拟议研究的逻辑目标是从现有资源中创建一项关于衰老的一个重要方面--身体成分变化的遗传流行病学研究。分析的目标是阐明与年龄相关的身体成分变化的遗传结构，广义上包括(并承认骨、肌肉和脂肪、心肺功能、血脂和激素的相互关联)指标。拟议研究的家庭数据将包括作为目前进行的四项研究的一部分收集的数据，以及将专门从这些研究参与者及其亲属那里收集的数据。这些研究是FELS纵向研究、高血压遗传学随访研究、2000年健康评估研究和骨质疏松风险研究。拟议的研究有三个具体目标：1)血统的组织和扩展--将侧重于40岁及以上的个人；将选择招募的个人，以最大限度地增加他们与其亲属之间的关系数量；2)数据组织和扩展--将侧重于与特定疾病风险有关的身体成分和相关特征的量化测量，包括骨质疏松症风险(例如骨密度)、超重和肥胖(例如身体脂肪百分比)、骨质疏松症(例如脱脂体重)、心肺功能(例如心率、血压和摄氧量)以及心血管疾病(例如脂质和内分泌分析)；3)统计遗传分析--将从横断面数据的单变量定量遗传分析，到横断面和纵向数据的多变量定量遗传分析，再到数据子集中横断面和纵向数据的连锁分析。

Conducting a modern genetic epidemiologic study of aging poses formidable logistic and analytic challenges. The key logistic challenge is to have sufficient familial data from individuals aged from middle age on up; the key analytic challenge is that from the process of aging biologically meaningful phenotypes suitable for analysis must be obtained. Significant body composition changes occur in both men and women throughout their adult lives. These changes affect the amount of bone and muscle, and the amount and distribution of fat. These changes in body composition contribute to the risks for complex diseases such as osteoporosis, sarcopenia and heart disease. The logistic goal of the proposed study is to create from existing resources a genetic epidemiologic study of an essential aspect of aging-changes in body composition. The analytic goal is to elucidate the genetic architecture of age-related changes in body composition, broadly defined to include (and acknowledge the inter-relatedness of) measures of bone, muscle and fat, cardiopulmonary functioning, lipids and hormones. Familial data for the proposed study will consist of data collected as part of four currently conducted studies, and data to be specifically collected for the proposed study from these study participants and their relatives. These studies are the Fels Longitudinal Study, the Genetics of Hypertension Follow-Up Study, the Health Assessment 2000 Study, and the Osteoporosis Risk Study. The proposed study has three specific aims: 1) Pedigree organization and expansion - will focus on individuals 40 years of age and older; recruited individuals will be selected to maximize the number of relationships between them and their kin; 2) Data organization and expansion - will focus on quantitative measures of body composition and related traits that pertain to specific disease risks, including osteoporosis risk (e.g., bone mineral density), overweight and obesity (e.g., percent body fat), sarcopenia (e.g., fat-free mass), cardiopulmonary functioning (e.g, heart rate, blood pressure, and oxygen uptake), and cardiovascular disease (e.g., lipid and endocrine assays); and 3) Statistical genetic analyses - will proceed from univariate quantitative genetic analyses of cross-sectional data, to multivariate quantitative genetic analyses of cross-sectional and longitudinal data, to linkage analyses of both cross- sectional and longitudinal data in a subset of the data.