Statistical Genetics of Outcomes and Drug Response in Patients with Type 2 Diabetes.

2 型糖尿病患者的结果和药物反应的统计遗传学。

• 批准号: 10928613
• 负责人: Alison Motsinger-Reif
• 金额: $ 15.05万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 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/10928613
• 关键词: Antihypertensive Agents; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Cardiovascular system; Caring; Chromosome Mapping; Clinic; Clinical Trials; Collaborations; Coupled; Diabetes Mellitus; Diuretics; Dyslipidemias; Event; Failure; Genetic; Genetic Variation; Glycosylated Hemoglobin; Glycosylated hemoglobin A; Goals; High Density Lipoprotein Cholesterol; Hypertension; Individual; International; LDL Cholesterol Lipoproteins; Manuscripts; Measurement; Meta-Analysis; Non-Insulin-Dependent Diabetes Mellitus; Organ; Outcome; Participant; Patients; Pharmaceutical Preparations; Pharmacogenomics; Phenotype; Regimen; Research Personnel; Resistant Hypertension; Therapeutic; Trans-Omics for Precision Medicine; Triglycerides; Universities; Variant; Virginia; Work; blood glucose regulation; blood lipid; cardiovascular disorder risk; cardiovascular risk factor; cohort; comorbidity; diabetic; epidemiology study; fasting plasma glucose; genetic association; genome wide association study; improved; indexing; individual response; medical schools; mortality; non-diabetic; pharmacologic; response; sex

Led by Dr. John House, the group has two major subprojects. The first project involves the Action to Control Cardiovascular Risk in Diabetes (ACCORD) cohort and an emerging phenotype in diabetes care and management - hemoglobin glycation index (HGI). HGI captures unexplained variation between point and mean-based measurements of glucose control in diabetics and has been associated with many comorbidities in individuals with diabetes. John has found sex-based genetic associations with HGI (a first), and demonstrated these are different than associations of either fasting plasma glucose or HbA1c levels. John's second project is leading the genetic mapping of resistant hypertension (RHTN) in a meta analysis in The International Consortium for Antihypertensive Pharmacogenomics Studies (ICAPS). RHTN is defined as blood pressure that remains above 140/90 mmHg despite optimal use of three antihypertensive medications of different classes, including a diuretic1. Such patients are more likely to have a secondary cause and to suffer end-organ damage. John has conducted GWAS for RHTN in ACCORD, and the meta analysis from other participants. This manuscript is nearing completion with unique replicated associations in another independent cohort (TopMED). Additionally, we work with consortia that rely on trials and cohorts with similar outcomes for meta-analyses and replication efforts.

在约翰·豪斯博士的领导下，该小组有两个主要的子项目。第一个项目涉及控制糖尿病心血管风险行动（雅阁）队列和糖尿病护理和管理中的新兴表型-血红蛋白糖化指数（HGI）。HGI捕获糖尿病患者血糖控制的基于点和基于平均值的测量之间的无法解释的变化，并且与糖尿病患者的许多合并症相关。John发现了基于性别的遗传与HGI的关联（第一次），并证明这些与空腹血糖或HbA 1c水平的关联不同。 John的第二个项目是在国际抗高血压药物基因组学研究联盟（ICAPS）的Meta分析中领导顽固性高血压（RHTN）的遗传图谱。RHTN定义为尽管最佳使用三种不同类别的降压药物（包括利尿剂），但血压仍高于140/90 mmHg 1。这类患者更有可能有继发性原因，并遭受终末器官损伤。John在雅阁中对RHTN进行了GWAS，并对其他参与者进行了Meta分析。该手稿即将完成，在另一个独立队列（TopMED）中具有独特的重复关联。 此外，我们与依赖于具有相似结果的试验和队列的联盟合作进行荟萃分析和复制工作。