Genetic Modulations of Morbidity Compression: A Population-Based Study

发病率压缩的基因调节：一项基于人群的研究

• 批准号: 9349627
• 负责人: P.J. ERIC STALLARD
• 金额: $ 79.34万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9349627
• 关键词: Activities of Daily Living; Address; Age; Aging; Biochemical Genetics; Biological Assay; Blood; Cessation of life; Chronic Disease; Communities; Comorbidity; Computer software; Constitutional; Consultations; Coupled; DNA; Data; Data Collection; Databases; Disease; Elderly; FOXO3A gene; FRAP1 gene; Genes; Genetic; Genetic Polymorphism; Genetic study; Genome; Genomics; Genotype; Gerontology; Health; Health Care Costs; Health Surveys; Heart Diseases; Heterozygote; Human; Hybrid Vigor; IGF1 gene; Impaired cognition; Impairment; Individual; Information Systems; Institutional Review Boards; Insulin; Life; Life Cycle Stages; Link; Long-Term Care; Longevity; Malignant Neoplasms; Measures; Medicaid; Medicare; Medicare claim; Medicare/Medicaid; Morbidity - disease rate; Participant; Pathway interactions; Persons; Phenotype; Physiological; Population; Protocols documentation; Publishing; Reporting; Research; Retirement; SNP array; SOD2 gene; Sample Size; Sampling; Sampling Studies; Siblings; Signal Transduction; Societies; Surveys; Swab; System; TP53 gene; Testing; Time; Triage; Uncertainty; Universities; Variant; Vital Statistics; Washington; Weight; Work; aged; base; bead chip; biodemography; cardiovascular health; cognitive function; comparative; cost; density; design; disability; eligible participant; end of life; follow-up; functional decline; functional improvement; genetic association; genetic information; genome wide association study; health data; health economics; indexing; instrumental activity of daily living; meetings; mortality; non-genetic; phenotypic data; population based; population survey; programs; public health relevance

 DESCRIPTION (provided by applicant): Human longevity steadily increased over the past century. There is great uncertainty, however, regarding the extent to which this was accompanied by the compression of morbidity. Given current dramatic increases in health care costs, especially costs during the last 6 months of life, this question is of profound importance t society. The National Long Term Care Survey (NLTCS) is a Medicare-based sample of the U.S. population aged 65+ initiated in 1982 with longitudinal follow-up in 1984, 1989, 1994, 1999, and 2004, with complete linkage to Medicare claims and vital statistics data for 1982-2009, and for eligible participants to Medicaid files (i.e., the 2004-2007 MAX files), supplemented with the 1999-2009 MDS and OASIS files. The 1982-1994 NLTCS produced the first reported major improvements of functional health as assessed by Activities of Daily Living (ADL) and Instrumental ADL (IADL) scores within the NLTCS population. The 1999 NLTCS substantially expanded its scope by selecting 1,877 participants and 869 siblings for supplemental data collection in 2000- 2002, yielding 639 blood (participants only) and 2,078 buccal swab (participants and siblings) samples for genetic studies. Moreover, of the 1,808 NLTCS participants contributing to the biospecimen sample, 1,345 were alive at the 2004 NLTCS and 1,183 were re-assessed. A total of 1,031 participants were age 85+ initially (429) or attained age 85 during the 2000-2010 follow-up period (602), with a total of 717 still alive as of the cutof date in 2010. The biospecimen sample currently provides 13,303 person-years of follow-up data, with 5,098 person-years above age 85. We propose to utilize this unique population-based sample, its associated functional data, linked Medicare/Medicaid claims data, and DNA samples, to quantitate variable degrees of the compression of morbidity and to test the hypothesis that constitutional genetic factors contribute to the modulation of these differential ratios of healthspans/lifespans. We will first address the connections between longevity, co-morbidity, functional health (ADL/IADL), and declines of physiological and cognitive functions (Aim 1). We will then conduct SNP array analysis of 639 blood and 2,078 buccal swab samples to obtain and assess a wide range of genetic information (Aim 2). We will assess associations of phenotypes of long healthy life with candidate polymorphisms within two highly relevant coupled gene networks-Insulin/IGF1 signaling (incl. FOXO3A and IGFR) and mTOR pathways-linked to aging and longevity across different species (Aim 3). Then, given published associations of genome-wide heterozygosity with cardiovascular health (Campbell et al., 2007), we will seek such associations with degrees of morbidity compression (Aim 4). Also, given the scientific value of the project data, we will release additional years of de-identified CMS data (Aim 5) and de- identified versions of the genotypic/phenotypic data derived from our SNP array analysis (Aim 6), using CMS, NIA, and Duke IRB approved protocols. We will replicate/validate our results using data from the Health and Retirement Study (HRS), employing comparable phenotypic and genotypic measures and linked CMS data.

 描述（适用提供）：过去一个世纪的人类长寿在稳步增长。然而，关于通过压缩发病率实现的程度，存在很大的不确定性。鉴于目前的医疗保健成本急剧增加，尤其是在生命的最后6个月中的成本，这个问题至关重要。国家长期护理调查（NLTCS）是1982年启动的65岁以上美国人口的基于医疗保险的样本，并于1984年，1984年，1989年，1994年，1994年，1999年和2004年进行纵向随访，与Medicare索赔和1982 - 2009年的Medicare索赔和生命统计数据完全联系，以及与Medicaid Files的合格参与者（I.99 MAXTENT MAXENDENT）（I. 2004和2004年7月7日），以及2004年2月7日，以及绿洲文件。 1982 - 1994年的NLTCS产生了第一个报道的功能健康的重大改善，这是通过NLTCS人群中日常生活（ADL）和仪器ADL（IADL）分数评估的。 1999年的NLTC在2000年至2002年间选择了1,877名参与者和869个兄弟姐妹，从而大大扩大了其范围，从而获得了2000年至2002年的补充数据收集，从而产生639名血液（仅参与者）和2,078个Buccal拭子（参与者和兄弟姐妹）样本进行遗传研究。此外，在2004年NLTC的1,808名NLTC参与者中，有1,345个还活着，并重新评估了1,183名。在2000-2010的随访期（602）期间，总共1,031名参与者年龄在85岁以上或年龄85岁以上（602），总共有717个还活着，截至2010年，生物相似样本目前为13,303人提供了13,303人年的随访数据，与5,098岁以上的年龄相关，我们将与85岁以上的人联系。 （ADL/IADL），并降低了物理和认知功能（AIM 1）。然后，我们将对639个血液和2,078个颊拭子样品进行SNP阵列分析，以获取和评估广泛的遗传信息（AIM 2）。我们将在两个高度相关的耦合基因网络 - 胰岛素/IGF1信号传导（含FOXO3A和IGFR）和MTOR途径中以及与不同物种的老化和寿命链接到衰老的两个高度相关的耦合基因网络 - 胰岛素/IGF1信号传导（包括FOXO3A和IGFR）的两个高度相关的耦合基因网络 - 胰岛素/IGF1信号（AIM 3）。然后，鉴于全基因组杂合性与心血管健康的已发表关联（Campbell等，2007），我们将寻求与发病程度压缩程度的关联（AIM 4）。此外，鉴于项目数据的科学价值，我们将使用CMS，NIA和Duke IRB批准的协议释放更多年的DE识别CMS数据（AIM 5）和DE鉴定版本的基因型/表型数据（AIM 6）。我们将使用可比的表型和基因型测量方法以及链接的CMS数据来复制/验证我们的结果。