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

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(ACCORD)队列和糖尿病护理和管理中的一种新表型--血红蛋白糖化指数(HGI)。HGI捕捉了糖尿病患者血糖控制的点和均值测量之间无法解释的差异，并已与糖尿病患者的许多共病相关。John发现了基于性别的基因与HGI的关联(首次)，并证明了这些与空腹血糖或HbA1c水平的关联是不同的。 John的第二个项目是在国际抗高血压药物基因组研究联盟(ICAPS)的荟萃分析中领导难治性高血压(RHTN)的基因图谱。RHTN的定义是血压保持在140/90毫米汞柱以上，尽管最佳使用了三种不同类别的降压药，包括利尿剂1。这类患者更有可能有继发性原因，并遭受终末器官损害。John在ACCORD中为RHTN进行了GWAS，并从其他参与者那里进行了Meta分析。这份手稿即将完成，在另一个独立的队列中具有独特的重复关联(TopMED)。 此外，我们与依赖试验和队列的财团合作，这些试验和队列具有类似的荟萃分析和复制努力。

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.