GENETIC EPIDEMIOLOGY OF AGING AND BODY COMPOSITION

对衰老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以上的个体中获得足够的家族数据;关键的分析挑战是必须从衰老的过程中获得适合分析的生物学上有意义的表型。 男性和女性在整个成年生活中都会发生显著的身体成分变化。 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。 这些身体成分的变化会增加患上骨质疏松症、肌肉减少症和心脏病等复杂疾病的风险。这项研究的逻辑目标是从现有的资源中创建一个遗传流行病学研究的一个重要方面的老化-身体组成的变化。 分析目标是阐明与年龄相关的身体组成变化的遗传结构，广义上包括骨骼，肌肉和脂肪，心肺功能，脂质和激素的测量（并承认其相互关联）。拟定研究的家族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，以及从这些研究受试者及其亲属中专门为拟定研究收集的数据。 这些研究包括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）谱系组织和扩展-将侧重于40岁及以上的个体;招募的个体将被选择以最大化他们与亲属之间的关系数量; 2）数据组织和扩展-将侧重于身体组成和与特定疾病风险相关的相关特征的定量测量，包括骨质疏松症风险（例如，骨矿物质密度），超重和肥胖（例如，体脂百分比），肌肉减少症（例如，无脂肪质量），心肺功能（例如，心率、血压和氧摄取），和心血管疾病（例如，脂质和内分泌测定）;和3）统计遗传分析-将从横截面数据的单变量定量遗传分析，到横截面和纵向数据的多变量定量遗传分析，再到数据子集中横截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.