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

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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.