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）中进行分析 评估糖尿病并发症与遗传之间关联的数据库 变体。 AIM 1涉及将创建虚拟基线的数据库开发 检查将MVP数据与VAMC门诊访问联系起来的检查，并在适当的情况下进行VAMC 住院，使用电子健康记录。我们将进行最前沿 共同（CVA）和罕见（RVA）的基因组广泛关联研究（GWAS） 变体。调查的结果是糖尿病眼，肾脏和心血管 并发症和低血糖。 AIM 2是糖尿病并发症分析 关于风险因素的纵向度量，关于结果风险的风险 （RF）包括遗传变异和传统RF，考虑单一和单一的RF 对横截面和周期患病率的结果进行多次评估 估计。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。具体结果 调查：眼（视网膜疾病，青光眼），肾脏（微珠和巨蛋白尿， 并减少EGFR [CKD阶段和ESRD），心血管衰竭（心脏衰竭）和 低血糖（急诊科和住院治疗，已针对HBA1C进行调整 和葡萄糖水平，以及（来自EHR）的血糖药物的使用）。目标3意志 发展糖尿病并发症风险评分。传统的RF和分开 对于每个结果，将使用逻辑回归比较遗传预测模型。 模型将评估RFS和药理疗法对血液异常的作用 压力，脂质和葡萄糖。我们将使用特定结果的遗传评分作为 潜在重新分类变量。