Aging-related Traits and Disease Risk Factors in a Sardinian Population Cohort

撒丁岛研究人群队列包括来自撒丁岛四个城镇集群的6200多名年龄在19岁至102岁之间的受试者。这项研究一直在测量200个二分性特征(吸烟等)。以及98个数量性状(内表型或与风险相关的数量遗传或环境因素)，可以在连续的尺度上进行评分。特别令人感兴趣的特征包括一系列心血管风险因素、人体测量、血液测试值和个性方面。 在这个队列中，使用多达100万个单核苷酸标记的电池进行了全基因组扫描，全基因组关联扫描(Gwas)指向了基因/变异，这些基因/变异决定了所研究的每个性状的遗传变异的很大一部分。随着财团在其他人群队列上的努力，包括巴尔的摩老龄化纵向研究和NIA支持的Inchianti研究，越来越多的出版物确定了与肥胖、心血管特征以及血脂和血液成分水平有关的基因。特别是，与尿酸作为心血管风险因素和与HBF水平作为地中海贫血/镰状细胞疾病严重程度调节因子的基因已经确定，还发现了决定身高的遗传因素以及与确定维生素B6、维生素B12、叶酸、同型半胱氨酸和尿酸水平有关的重要基因：确定心血管风险因素，包括心脏复极中的磷蛋白、动脉僵硬中的COL4A1、血压的基因位点，许多因素影响肥胖；以及影响体重过轻和超重的个性因素的发现(完整列表见参考文献)。 研究队列的其他访问正在进行中，以允许评估纵向趋势和结果，以及评估与年龄相关的骨密度和脆弱程度的其他表型。例如，正在进行24小时血压测量，正在分析饮食，正在通过光学扫描测量头部的形态特征。在一个互补的方法中，遗传学研究正在扩展到撒丁岛患者的临床系列和几种疾病的对照，包括乳腺癌和自身免疫性疾病，所有这些疾病在岛上的发病率都非常高。在一份关于多发性硬化症的初步报告中，发现了一种基因(CBLB)，它调节撒丁岛和其他人群以及该疾病的小鼠模型中的免疫反应水平。

The SardiNIA study population cohort comprises over 6,200 subjects, aged 19-102, from a cluster of four towns in Sardinia. The study has been measuring >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. Traits of special interest include a range of cardiovascular risk factors, anthropometric measurements, blood test values, and facets of personality. With this cohort, full-genome scans with batteries of up to 1,000,000 single-nucleotide markers were conducted, and genome-wide association scans (GWAS) have pointed to genes/variants that determine a significant portion of the genetic contribution to variance for each trait studied. In conjunction with consortium efforts on other population cohorts, including the Baltimore Longitudinal Study of Aging and the InCHIANTI study supported by the NIA, an increasing number of publications have resulted that identify genes associated with obesity, cardiovascular traits, and levels of lipids and blood components. In particular, genes associated with uric acid as a cardiovascular risk factor and with HbF levels as a modulator of thalassemia/sickle cell disease severity have been identified, as well as findings of genetic factors determining height as well as significant genes involved in determining the levels of vitamin B6, vitamin B12, folate, homocysteine, and uric acid: the identification of cardiovascular risk factors that include phospholambin in cardiac repolarization, Col4A1 in arterial stiffness, loci for blood pressure, many affecting adiposity; and findings of personality facets affecting under- and over-weight (see bibliography for a complete list). Additional visits are in process 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. For example, 24 hour blood pressure measurements are being made, diet is being analyzed, and morphological features of the head are being measured by optical scans. In a complementary approach, the genetic studies are being extended to clinical series of Sardinian patients and controls for several diseases, including breast cancer and autoimmune diseases, all of which have a very high incidence on the island. In an initial report on multiple sclerosis, a gene was identified (CBLB) that regulates the level of the immune response both in patients in Sardinia and in other populations and in a mouse model for the disease.