We developed a smartphone application, MyGeneRank, to conduct a prospective observational cohort study (NCT03277365) involving the automated generation, communication, and electronic capture of response to a polygenic risk score (PRS) for coronary artery disease (CAD). Adults with a smartphone and an existing 23andMe genetic profiling self-referred to the study. We evaluated self-reported actions taken in response to personal CAD PRS information, with special interest in the initiation of lipid-lowering therapy. 19% (721/3,800) of participants provided complete responses for baseline and follow-up use of lipid-lowering therapy. 20% (n = 19/95) of high CAD PRS vs 7.9% (n = 8/101) of low CAD PRS participants initiated lipid-lowering therapy at follow-up (p-value = 0.002). Both the initiation of statin and non-statin lipid-lowering therapy was associated with degree of CAD PRS: 15.2% (n = 14/92) vs 6.0% (n = 6/100) for statins (p-value = 0.018) and 6.8% (n = 8/118) vs 1.6% (n = 2/123) for non-statins (p-value = 0.022) in high vs low CAD PRS, respectively. High CAD PRS was also associated with earlier initiation of lipid lowering therapy (average age of 52 vs 65 years in high vs low CAD PRS respectively, p-value = 0.007). Overall, degree of CAD PRS was associated with use of any lipid-lowering therapy at follow-up: 42.4% (n = 56/132) vs 28.5% (n = 37/130) (p-value = 0.009). We find that digital communication of personal CAD PRS information is associated with increased and earlier lipid-lowering initiation in individuals of high CAD PRS. Loss to follow-up is the primary limitation of this study. Alternative communication routes, and long-term studies with EHR-based outcomes are needed to understand the generalizability and durability of this finding.
Essential tremor (ET) and Parkinson's disease (PD) are among the most common adult-onset tremor disorders. Clinical and pathological studies suggest that misdiagnosis of PD for ET, and vice versa, occur in anywhere from 15% to 35% of cases. Complex diagnostic procedures, such as dopamine transporter imaging, can be powerful diagnostic aids but are lengthy and expensive procedures that are not widely available. Preliminary studies suggest that monitoring of tremor characteristics with consumer grade accelerometer devices could be a more accessible approach to the discrimination of PD from ET, but these studies have been performed in well-controlled clinical settings requiring multiple maneuvers and oversight from clinical or research staff, and thus may not be representative of at-home monitoring in the community setting. Therefore, we set out to determine whether discrimination of PD vs. ET diagnosis could be achieved by monitoring research subject movements at home using consumer grade devices, and whether discrimination could be improved with the addition of genetic profiling of the type that is readily available through direct-to-consumer genetic testing services. Forty subjects with PD and 27 patients with ET were genetically profiled and had their movements characterized three-times a day for two weeks through a simple procedure meant to induce rest tremors. We found that tremor characteristics could be used to predict diagnosis status (sensitivity = 76%, specificity = 65%, area under the curve (AUC) = 0.75), but that the addition of genetic risk information, via a PD polygenic risk score, did not improve discriminatory power (sensitivity = 80%, specificity = 65%, AUC = 0.73).
