Genetics of Type 2 Diabetes: Opportunities for Precision Medicine

Type 2 diabetes (T2D) is highly prevalent and a strong contributor for cardiovascular disease (CVD). However, there is significant heterogeneity in disease pathogenesis and the risk of complications. Enormous progress has been made in our ability to catalog genetic variation associated with T2D-risk and variation in disease relevant quantitative traits. These discoveries hold the potential to shed light on tractable targets and pathways for safe and effective therapeutic development, but the promise of precision medicine has been slow to be realized. Recent studies have identified subgroups of individuals with differential risk for intermediate phenotypes (e.g., lipid levels, fasting insulin, BMI), which contribute to T2D risk, helping to account for the observed clinical heterogeneity. These “partitioned genetic risk scores” have not only the potential to identify patients at greatest risk of CVD and rapid disease progression, but could also aid patient stratification bridging the gap towards precision medicine for T2D.