Heritability and Covariate Traits-Sardinian/Other Cohort

为了确定年龄相关特征中的遗传和流行病学因素，我们正在应用新的统计方法来寻找大型人口数据集中的协变量和隐藏的相关性。一个特别的重点是国家情报局赞助的创始人撒丁岛人口的研究，其中相互关联和稳定的环境，人口在许多代可以简化分析。该研究已经对>200个二分特征（吸烟等）进行了评分。和98个数量性状（“内表型”或“数量风险相关的遗传或环境因素”），可以在连续量表上评分。数量性状的使用允许研究群体中等位基因变异的整个范围。特别感兴趣的特征包括一系列心血管危险因素，人体测量，血液测试值和个性方面。 在目前为期5年的合同中，撒丁岛的一个科学家团队从撒丁岛中东部的四个城镇中招募了6,100多名受试者，并测量了每个受试者的所有特征。该地区14-102岁的人口中有一半以上是在当地出生的，至少96%的人的祖父母都出生在同一个省。该群体包括4933个表型同胞对，4266个表型亲子对，>4069个表型表亲对，以及超过6459个表型伯父对。这个样本足够大，表型足够好，足以表明即使在这个创始人群体中，个体性状的方差也与远交群体相当;它足够大，相互关联，足以推断性状遗传力的高度显著估计。全基因组扫描（基因分型）应该有能力检测出贡献性状变异10%的基因座。在这个队列中，正在进行一系列单核苷酸标记的全基因组扫描。此外，已开始对研究队列进行第二次访视，以评估纵向趋势和结局，以及评估与骨密度和脆弱性相关的其他表型（作为年龄的函数）。 虽然人口的基因组扫描开始寻找参与决定特定性状的基因，但在这个子项目中正在进行有针对性的数据分析，以寻找相关/重叠的遗传和流行病学因素，包括意外的相关性，并将可能的相关性与其他大型人口队列研究进行比较，包括巴尔的摩老龄化纵向研究。

With the goal of determining genetic and epidemiological factors in age-related traits, we are applying new statistical approaches to look for covariates and hidden correlations in large population data sets. A particular focus is the NIA-sponsored study of the founder Sardinian population, where inter-relatedness and stable environment of the population over many generations can simplify the analysis. The study has been scoring >200 dichotomized traits (smoking, etc.) and 98 quantitative traits ("endophenotypes" or "quantitative risk-related genetic or environmental factors") that can be scored on a continuous scale. The use of quantitative traits permits the study of the entire range of allelic variation in a population. Traits of special interest include a range of cardiovascular risk factors, anthropometric measurements, blood test values, and facets of personality. In a current 5-year contract, a team of Sardinian scientists has recruited over 6,100 subjects from a selected group of four towns in east-central Sardinia, and has measured all traits for each subject. The sample cohort numbers over half of the population of the region aged 14-102; they are native-born, and at least 96 percent are known to have all grandparents born in the same province. The group include 4933 phenotyped sib pairs, 4266 phenotyped parent-child pairs, >4069 phenotyped cousin pairs, and more than 6459 phenotyped avuncular pairs. This sample is large enough and well enough phenotyped to show that even in this founder population, the variance for individual traits is comparable to that in outbred populations; and it is large enough and interrelated enough to infer highly significant estimates of genetic heritability for traits. Genome-wide scans (genotyping) should have the power to detect loci that contribute the order of 10 percent of variance for a trait. With this cohort, full-genome scans with batteries of single-nucleotide markers are being carried out. In addition, second visits have been initiated for the study cohort to permit the assessment of longitudinal trends and outcomes, as well as the assessment of additional phenotypes related to bone density and frailty as a function of age. While the genome scans of the population begin to search for genes involved in the determination of particular traits, targeted data analysis is being done in this subproject to look for correlated/overlapping genetic and epidemiological factors, including unexpected correlations, and to compare possible correlations with other large population cohort studies, including the Baltimore Longitudinal Study of Aging.