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

SardiNIA研究人群队列包括来自撒丁岛四个城镇的6，200多名受试者，年龄在19-102岁之间。这项研究已经测量了超过200个二分法特征（吸烟等）。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。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。 在这个队列中，使用多达1，000，000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）指出了决定每个研究性状变异遗传贡献的重要部分的基因/变异。与其他人群队列的联盟努力相结合，包括巴尔的摩老龄化纵向研究和由NIA支持的InCHIANTI研究，越来越多的出版物鉴定了与肥胖、心血管特征、血脂和血液成分水平相关的基因。特别地，已经鉴定了与作为心血管风险因素的尿酸和作为地中海贫血/镰状细胞病严重程度的调节剂的HbF水平相关的基因，以及确定身高的遗传因素的发现以及参与确定维生素B6、维生素B12、叶酸、同型半胱氨酸和尿酸水平的重要基因：确定心血管危险因素，包括心脏复极化中的受磷蛋白、动脉僵硬度中的Col 4A 1、血压位点，许多影响肥胖;以及影响体重不足和超重的个性方面的研究结果（完整列表见参考书目）。 正在对研究队列进行额外访视，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）。例如，正在进行24小时血压测量，正在分析饮食，并且正在通过光学扫描测量头部的形态特征。 作为补充，遗传研究正在扩大到撒丁岛病人的临床系列和几种疾病的控制，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很高。在关于多发性硬化症的初步报告中，确定了一种基因（CBLB），该基因调节撒丁岛和其他人群患者以及该疾病小鼠模型的免疫反应水平。

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.