STRONG HEART FAMILY STUDY

强心家庭研究

• 批准号: 6185320
• 负责人: JEAN W MACCLUER
• 金额: $ 47.85万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-10 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6185320
• 关键词: Native Americans; blood chemistry; cardiovascular disorder; cardiovascular disorder epidemiology; clinical research; cooperative study; disease /disorder proneness /risk; family genetics; genetic polymorphism; genetic screening; genetic susceptibility; human subject; linkage mapping; quantitative trait loci; urinalysis

The long-term goal of the Strong Heart Family Study is to detect and map polymorphic genes that influence variation in risk factors for cardiovascular disease and other related disorders that are major health problems in American Indians. Of immediate interest are risk factors and precursors such as plasma concentrations of lipoproteins, apolipoproteins, insulin, glucose, urine albumin excretion, measures of obesity, measures associated with hemostasis, and measures of cardiac and arterial structure and function. In the pilot study during the current grant period, we have collaborated with the other Strong Heart Study (SHS) investigators in successfully recruiting and examining more than 300 members of extended families in each of the three centers (in Arizona, Oklahoma, and the Dakotas). We have shown that many of the CVD-related phenotypes are heritable, and we are generating a 10 centimorgan map that we are using in preliminary linkage analysis to localize CVD risk factor genes. We are encouraged by the success of the pilot study. To provide adequate power to detect and map CVD risk factor genes in each center and to localize genes that are important across tribal groups, we propose to recruit 900 additional members of approximately 30 extended families in each center, ascertained through SHS participants. We will estimate heritabilities, effects of covariates, household and center effects, and genetic and environmental correlations for a large set of CVD risk factor phenotypes. We will generate a 10 centimorgan map that includes genotyping of 386 short tandem repeats (STRs) in each of the 2700 individuals, and screen the phenotypes for linkage using a variance component approach. We will do finer scale mapping with additional STRs to more precisely localize quantitative trait loci (QTLs) within targeted chromosomal regions, and use SNPs in positional candidate genes for linkage/association analysis to identify genes that are responsible for linkages detected by the initial genome scan. The Southwest Foundation investigators will continue to direct the design of the Family Study, will identify families to recruit, will serve as a resource for questions concerning recording of family data, directions in which to expand families, etc., and will be responsible for genotyping and statistical genetic analysis. This study will form the basis for future studies aimed at identifying and characterizing the genes that influence CVD risk factors in American Indians.

强心脏家族研究的长期目标是检测和定位影响心血管疾病和其他相关疾病风险因素变异的多态基因，这些疾病是美国印第安人的主要健康问题。直接感兴趣的是危险因素和先兆，如血浆脂蛋白、载脂蛋白、胰岛素、葡萄糖、尿白蛋白排泄的浓度、肥胖指标、止血措施以及心脏和动脉结构和功能的指标。在当前资助期的试点研究中，我们与其他强心研究(SHS)研究人员合作，成功地招募和检查了三个中心(亚利桑那州、俄克拉何马州和达科他州)每个中心的300多名大家庭成员。我们已经证明了许多与心血管疾病相关的表型都是可遗传的，我们正在生成一个10厘米的图谱，我们正在使用该图谱进行初步的连锁分析，以定位心血管疾病危险因素基因。我们对试点研究的成功感到鼓舞。为了提供足够的能力来检测和定位每个中心的心血管疾病危险因素基因，并定位跨部落群体的重要基因，我们建议在每个中心招募大约30个大家庭的900名额外成员，通过SHS参与者确定。我们将评估一大组心血管疾病危险因素表型的遗传力、协变量效应、家庭和中心效应以及遗传和环境相关性。我们将生成一个10厘米的图谱，其中包括2700个个体中每个个体的386个短串联重复(STR)的基因分型，并使用方差分量方法筛选连锁的表型。我们将利用额外的STR进行更精细的比例定位，以更精确地定位目标染色体区域内的数量性状基因座(QTL)，并使用位置候选基因中的SNP进行连锁/关联分析，以确定负责初始基因组扫描检测到的连锁的基因。西南基金会调查人员将继续指导家庭研究的设计，将确定要招募的家庭，将作为有关家庭数据记录、扩大家庭的方向等问题的资源，并将负责基因分型和统计遗传分析。这项研究将为未来的研究奠定基础，这些研究旨在识别和表征影响美洲印第安人心血管疾病风险因素的基因。