HERITAGE-GENETICS, RESPONSE TO EXERCISE, RISK FACTORS-3

HERITAGE家族研究的目的是记录耐力训练的心血管和代谢反应，以及遗传因素对心血管疾病（CVD）和2型糖尿病风险因素的伴随反应的贡献。 在第一阶段（1992年至1997年），855久坐不动的受试者从218个家庭和742名受试者（483名白人从99个家庭，259名黑人从105个家庭）完成了一个标准化的20周的运动训练计划。 在第2阶段（1997-2001），进行了一系列非遗传研究的心肺耐力的决定因素，心血管疾病和2型糖尿病的危险因素，在久坐状态和训练的反应。 遗传分析的重点是确定遗传力水平，并测试父或母的影响，主基因效应和分离模式。 一组候选基因被分型用于关联和连锁研究。 对心肺耐力、心血管疾病和2型糖尿病危险因素的训练反应进行了全基因组扫描。 拟议的第三阶段围绕五个具体目标组织。 首先，将调查与主要心血管疾病危险因素的训练相关变化有关的遗传流行病学问题，特别强调黑人和白色人的差异。 其次，基因和突变的搜索将继续利用四种策略：全基因组扫描的扩展，包括有针对性的密集SNPs定位，扩展骨骼肌基因表达研究与SAGE，使用AFLP技术和使用新的统计方法，如多变量连锁方法，亚组分析，和全基因组连锁测试。 第三，胰岛素敏感性，胰岛素分泌和葡萄糖有效性的遗传和非遗传决定因素的培训将使用LONGMOD，MINMOD的扩展，目前正在开发的模型纵向数据更有效地进行调查。 第四，将调查目标心血管疾病危险因素的非遗传决定因素及其对耐力训练的反应，重点是黑人和白色人的差异。 第五，我们将评估一个密切监督的20周定期锻炼是否对习惯性体力活动水平和健康状况有任何长期影响。 来自HERITAGE家族研究第3期的结果将提供关于身体活动生活方式的益处以及黑人和白人高和低反应表型的决定因素的独特信息。 本申请由彭宁顿生物医学研究中心提交，该中心也是遗产联盟协调中心。

The aim of the HERITAGE Family Study is to document the cardiovascular and metabolic responses to endurance training, and the contribution of genetic factors to the concomitant response of cardiovascular disease (CVD), and type 2 diabetes risk factors. In Phase 1 (1992-1997), 855 sedentary subjects from 218 families were recruited and 742 subjects (483 Whites from 99 families, 259 Blacks from 105 families) completed a standardized 20-week exercise-training program. During Phase 2 (1997-2001), a series of non-genetic studies on determinants of cardiorespiratory endurance, and CVD and type 2 diabetes risk factors in the sedentary state and in the response to training were undertaken. Genetic analyses focused on the determination of the heritability levels, and testing for paternal or maternal effects, major gene effects and segregation patterns. A panel of candidate genes was typed for association and linkage studies. A genome-wide scan was performed for the training response of cardiorespiratory endurance and CVD and type 2 diabetes risk factors. The proposed Phase 3 is organized around five specific aims. First, genetic epidemiology questions pertaining to training-related changes in major CVD risk factors will be investigated with special emphasis on Black and White differences. Second, the search for genes and mutations will continue utilizing four strategies: extension of the genome-wide scan including targeted dense SNPs mapping, extension of the skeletal muscle gene expression studies with SAGE, use of the AFLP technique and use of novel statistical methods such as multivariate linkage methods, subgroup analyses, and total genome-wide linkage tests. Third, the genetic and non-genetic determinants of insulin sensitivity, insulin secretion and glucose effectiveness in response to training will be investigated using LONGMOD, an extension of MINMOD currently in development to model longitudinal data more efficiently. Fourth, the nongenetic determinants of the targeted CVD risk factors and their responses to endurance training will be investigated, with emphasis on Black and White differences. Fifth, we will assess whether a closely supervised 20-week period of regular exercise had any long-term effects on habitual physical activity levels and health status. The findings from Phase 3 of the HERITAGE Family Study will provide unique information on the benefits of a physically active lifestyle and on the determinants of the high and low response phenotypes in Blacks and Whites. This application is submitted from the Pennington Biomedical Research Center which also serves as the HERITAGE Consortium Coordinating Center.