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（由申请人提供）：在过去的世纪，人类寿命稳步增长。然而，在多大程度上伴随着发病率的压缩，这是很不确定的。鉴于目前医疗保健费用的急剧增加，特别是生命最后6个月的费用，这个问题对社会具有深远的重要性。国家长期护理调查（NLTCS）是1982年启动的基于Medicare的美国65岁以上人群样本，在1984年、1989年、1994年、1999年和2004年进行了纵向随访，与1982-2009年的Medicare索赔和生命统计数据完全关联，并为符合条件的参与者提供了Medicaid文件（即，2004-2007 MAX文件），并补充了1999-2009 MDS和OASIS文件。1982-1994年NLTCS首次报道了NLTCS人群中通过日常生活活动（ADL）和工具性ADL（IADL）评分评估的功能健康的重大改善。1999年的NLTCS大大扩大了其范围，在2000- 2002年期间选择了1，877名参与者和869名兄弟姐妹进行补充数据收集，产生了639份血液（仅参与者）和2，078份口腔拭子（参与者和兄弟姐妹）样本用于遗传研究。此外，在1，808名NLTCS参与者中，有1，345人在2004年NLTCS中存活，1，183人进行了重新评估。共有1，031名参与者最初年龄为85岁以上（429人）或在2000-2010年随访期间达到85岁（602人），截至2010年截止日期，共有717人仍然活着。生物样本目前提供了13,303人年的随访数据，其中5,098人年超过85岁。我们建议利用这个独特的基于人口的样本，其相关的功能数据，链接的医疗保险/医疗补助索赔数据，和DNA样本，量化的发病率的压缩程度的变量，并测试假设，体质遗传因素有助于这些差异比例的healthspans/寿命的调制。我们将首先讨论长寿，共病，功能健康（ADL/IADL）和生理和认知功能下降（目标1）之间的联系。然后，我们将对639份血液和2,078份口腔拭子样本进行SNP阵列分析，以获得和评估广泛的遗传信息（目标2）。我们将评估健康长寿的表型与两个高度相关的偶联基因网络中的候选多态性之间的关联-胰岛素/IGF 1信号传导（包括IGF 1信号传导）。FOXO 3A和IGFR）和mTOR通路-与不同物种的衰老和寿命相关（目的3）。然后，考虑到已发表的全基因组杂合性与心血管健康的关联（坎贝尔等人，2007），我们将寻求与发病率压缩程度的关联（目标4）。此外，考虑到项目数据的科学价值，我们将使用CMS、NIA和杜克IRB批准的方案，发布额外几年的去识别CMS数据（目标5）和来自SNP阵列分析的基因型/表型数据的去识别版本（目标6）。我们将使用健康和退休研究（HRS）的数据复制/验证我们的结果，采用可比的表型和基因型指标以及相关的CMS数据。