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

撒丁岛人群中的衰老相关特征和疾病危险因素

• 批准号: 8335890
• 负责人: David Schlessinger
• 金额: $ 37.49万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8335890
• 关键词: Affect; Age; Aging; Autoimmune Diseases; Baltimore; Bibliography; Biochemical; Blood Pressure; Blood Tests; Bone Density; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cholesterol; Clinical; Cohort Studies; Diet; Disease; Early Diagnosis; Environmental Risk Factor; Epidemiological Factors; Event; Folate; Genes; Genetic; Genetic Variation; Genome Scan; Goals; Head; Height; Homocysteine; Homocystine; Hour; Immune response; Incidence; Intervention; Island; Life; Longitudinal Studies; Measurement; Measures; Multiple Sclerosis; Nucleotides; Obesity; Optics; Outcome; Overweight; Patients; Personality; Phenotype; Population; Population Study; Process; Publications; Reporting; Risk; Risk Factors; Route; Sardinia; Scanning; Series; Severity of illness; Sickle Cell Anemia; Smoking; Thalassemia; Uric Acid; Visit; Vitamin B 12; Vitamin B6; Weight; age related; aged; arterial stiffness; blood lipid; cardiovascular risk factor; cohort; disorder risk; endophenotype; frailty; genome wide association study; interest; malignant breast neoplasm; mouse model; trait; trend

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.

萨迪尼亚研究人群队列组成的撒丁岛四个城镇的群体包括6,200多名，年龄在19-102年。该研究一直在测量200个二分法特征（吸烟等）和98个定量性状（内型特性或与风险相关的遗传因素或环境因素），可以连续得分。特殊兴趣的特征包括一系列心血管危险因素，人体测量值，血液测试值和人格的方面。 通过这种队列，进行了全基因组扫描，并进行了高达1,000,000个单核苷酸标记的电池，并且全基因组的关联扫描（GWAS）指出了基因/变体，这些基因/变体确定了每个特征研究的遗传学方差的很大一部分。结合了其他人群人群的联盟努力，包括NIA支持的巴尔的摩纵向研究和Inchianti研究，越来越多的出版物导致识别与肥胖，心血管性状性状以及脂质和血液成分水平相关的基因。特别是，已经确定了与尿酸作为心血管危险因素以及HBF水平作为丘脑/镰状细胞疾病严重程度的调节剂相关的基因，以及确定身高的遗传因素以及确定维生素B6的水平，维生素B12，生动物B12，易生酸，甲酸，uriric和Urric cy Irric和Urric Inciror：the the the the the the the the the the the the Irric and the the the the the the the Incor cons Incilection和by的遗传因素的发现，该基因的水平。心脏复极化中的磷脂，COL4A1在动脉僵硬中，血压的基因座，许多影响肥胖。以及影响不足和权重的人格方面的发现（有关完整列表，请参见参考书目）。 研究队列正在进行额外的访问，以评估纵向趋势和结果，并评估与年龄有关的与骨密度和脆弱相关的其他表型。例如，正在进行24小时的血压测量，正在分析饮食，并通过光学扫描来测量头部的形态特征。 在一种互补的方法中，遗传研究扩展到撒丁岛患者的临床系列，以及包括乳腺癌和自身免疫性疾病在内的多种疾病的对照组，所有这些疾病在岛上的发生率很高。在关于多发性硬化症的初步报告中，鉴定了一个基因（CBLB），该基因调节撒丁岛和其他人群的患者以及该疾病的小鼠模型中的免疫反应水平。