Questions, Behavior, and Responsibility in Precision Medicine

We are living in a unique time in history as the scientific community undergoes changes in behavior and technology to enable impactful discoveries from large data sets and clinical trials that include precision medicine. Impactful discoveries may arise from asking the most fundamental question through the eyes of a patient and choosing a new method of analysis. In this issue of Circulation, 2 new studies asked fundamental questions: “How does one use precise genetic information about an individual to predict a stroke?” and “How does one use precise genetic information about an individual to predict drug-induced long QT syndrome?”1,2 These 2 studies illustrate how behavioral changes in our community embracing data sharing and precision medicine clinical trials help solve these questions. Importantly, behavioral change is fundamental to opening the gates and delivering individuals precise knowledge about their health and precise solutions to prevent or cure a cardiovascular event or stroke. Atrial fibrillation affects 33.5 million individuals globally.3 The heritability of lone atrial fibrillation has been well established in the literature.4 Individuals with atrial fibrillation are at a significantly increased risk of stroke. However, many individuals with atrial fibrillation choose to avoid oral anticoagulation for reasons of healthcare costs, time, or uncertainty. These individuals may not connect atrial fibrillation with the significantly increased risk of stroke and may not recognize the importance of starting treatment to decrease the risk of stroke. From a healthcare perspective, identifying individuals at risk of stroke and providing preventive care has been challenging. In this issue of Circulation, Lubitz and a team of cross-disciplinary investigators1 sought to determine whether an individual’s genetic risk for atrial fibrillation could help predict the risk of cardioembolic stroke. Lubitz and colleagues included just over 18 000 individuals of self-reported European ancestry ranging from 58 to 75 years of age with the proportion of women ranging from 47% to 52% from all included cohorts.1 During 5 years of follow-up, 5.5% of the individuals developed incident atrial fibrillation. The atrial fibrillation genetic risk score for each individual was calculated by summing the dosage of each atrial fibrillation risk allele carried (ranging from 0–2) weighted by the natural algorithm of the relative risk for each single-nucleotide polymorphism (SNP). The 719 SNPs used in the study were derived from the pruning of 2.2 million HapMap variants included in a prior independent meta-analysis of genome-wide association studies for atrial fibrillation from the AFGen consortium (Atrial Fibrillation Consortium) and then further narrowed.5 The genetic risk score was tested on 5 prospective studies.1 The association between AF genetic risk and stroke was also examined in MGH-GASROS (Massachusetts General Hospital Genes Associated With Stroke and Outcomes Study) and referent individuals from the Myocardial Infarction Genetics Consortium. Questions, Behavior, and Responsibility in Precision Medicine