Diabetic Complications and Genetic Variants in the Million Veterans Program

百万退伍军人计划中的糖尿病并发症和遗传变异

• 批准号: 10268156
• 负责人: LAWRENCE S PHILLIPS
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-10-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10268156
• 关键词: Adult; African; Age; Albuminuria; Alleles; Atherosclerosis; Blood Pressure; Body mass index; Cardiovascular system; Clinical; Complications of Diabetes Mellitus; Custom; Data; Databases; Development; Diabetes Mellitus; Electronic Health Record; Emergency department visit; End stage renal failure; Ethnic Origin; European; Eye; Frequencies; Gene Frequency; Genes; Genetic; Genetic Databases; Genotype; Glaucoma; Glucose; Glycosylated hemoglobin A; Health; Healthcare; Heart failure; Hospitalization; Hypoglycemia; Infrastructure; Insulin-Dependent Diabetes Mellitus; Kidney; Link; Lipids; Logistic Regressions; Measurement; Measures; Medicare; Metabolic; Methods; Minor; Modeling; Non-Insulin-Dependent Diabetes Mellitus; Organ; Outcome; Outcome Assessment; Outpatients; Participant; Pharmaceutical Preparations; Pharmacology; Phenotype; Population; Positioning Attribute; Prevalence; Race; Recording of previous events; Records; Research Personnel; Resources; Retinal Diseases; Risk; Risk Factors; Role; Source; Validation; Variant; Veterans; Visit; biobank; cost; demographics; design; diabetic; ethnic minority population; genetic risk factor; genetic variant; genome wide association study; genome-wide; genome-wide analysis; improved; insertion/deletion mutation; multi-ethnic; personalized care; predictive modeling; programs; racial and ethnic; rare variant; time use; trait; virtual

We propose to undertake analyses within the Million Veterans Program (MVP) database to Assess Associations between Diabetic Complications and Genetic Variants. Aim 1 involves Database Development that will create a virtual baseline examination linking MVP data to VAMC outpatient visits, and, when appropriate, VAMC hospitalizations, using the electronic health record. We will conduct cutting edge Genome Wide Association Studies (GWAS) of common (CVAS) and rare (RVAS) variants. The outcomes investigated are diabetic eye, kidney, and cardiovascular complications, and hypoglycemia. Aim 2 is Diabetes Complications Analyses concerning outcome risks using time-integrated longitudinal measures of risk factors (RFs) to include both genetic variants and traditional RFs considering both single and multiple assessments of outcomes with cross-sectional and period prevalence estimates. We will analyze organ-specific and metabolic complications according to type 1 and type 2 diabetes status using EHR data in VA records. Specific outcomes investigated: Ocular (retinal disease, glaucoma), Renal (micro- and macro-albuminuria, and decreased eGFR [CKD stages and ESRD), Cardiovascular (cardiac failure), and Hypoglycemia (emergency department visits and hospitalizations, adjusted for HbA1c and glucose levels, and use of glycemic medications [from the EHR]). Aim 3 will develop Diabetic Complications Risk Scores. Both traditional RF and separate genetic prediction models will be compared using logistic regression for each outcome. Models will evaluate the role of RFs and pharmacologic therapy for abnormal blood pressure, lipids, and glucose. We will use an outcome-specific genetic score as a potential reclassification variable.

我们建议在百万退伍军人计划（MVP）内进行分析 评估糖尿病并发症与遗传之间关联的数据库 变体。目标1涉及创建虚拟基线的数据库开发 将MVP数据与VAMC门诊访视联系起来的检查，以及适当时，VAMC 使用电子健康记录进行住院治疗。我们将进行尖端的 常见（CVAS）和罕见（RVAS）的全基因组关联研究（GWAS） 变体。研究的结果是糖尿病的眼睛，肾脏和心血管 并发症和低血糖目的2：糖尿病并发症分析 关于使用风险因素的时间整合纵向测量的结果风险 (RFs)包括遗传变异和传统的RF，考虑到单一和 对具有横断面和时期患病率的结局进行多重评估 估算我们将根据类型分析器官特异性和代谢并发症 1和2型糖尿病状态使用VA记录中的EHR数据。具体成果 检查：眼部（视网膜疾病，青光眼），肾脏（微量和大量白蛋白尿， eGFR降低[CKD分期和ESRD）、心血管（心力衰竭）和 低血糖（急诊室访视和住院，根据HbA1c调整 和葡萄糖水平，以及血糖药物的使用[来自EHR]）。目标3将 制定糖尿病并发症风险评分。传统RF和分离式 遗传预测模型将使用逻辑回归对每个结果进行比较。 模型将评估RF和药物治疗对异常血液的作用。 血压血脂和葡萄糖我们将使用结果特异性遗传评分作为 潜在的重新分类变量。