The Geisinger MyCode® Community Health Initiative: Experiences in Patient Recruitment, Genomic Sequencing, and Patient Engagement in a Population-Based Biobank

Background/Aims: Geisinger’s MyCode® Community Health Initiative is a population-based biorepository that began in 2007. Participants give broad consent for research use of their samples and electronic health record data, including genomic analysis, and permission to re-contact for additional studies. Participation in MyCode is open to all Geisinger patients, with a goal to enroll 250,000 participants. In 2013, consent was revised to allow for return of medically actionable information discovered through genomic studies to patients and providers and to include the information in the electronic health record. In 2014, a collaboration was initiated with the Regeneron Genetics Center to perform whole exome sequencing on biobank samples. The Governing Board approves all research conducted on biobank specimens, the Return of Results Oversight Committee monitors the return of clinical findings, and the External Ethics Advisory Committee provides independent feedback on MyCode operations and the clinical return of results process. Community members are engaged through research focus groups, newsletters and as members of the two committees. Methods: MyCode is visible via signage throughout Geisinger clinics and system website. Approximately 20 MyCode consenters are stationed in outpatient clinics throughout the system. Samples are collected at the time of clinical blood draws. Consented participants who have not had clinical bloodwork may arrange to provide a MyCode sample if desired. Saliva collection may also be requested. In May 2015, an educational campaign was launched to ensure that all Geisinger employees can answer patient questions about biobank participation. Results: At this time, approximately 1,000 patients consent per week, 90,000 patients have consented (85% response rate), 55,000 have at least one sample in the biobank, and 50,000 exomes have been sequenced thus far. The population of consented patients is 97% white, 62% female and 50% aged 50–79 years. Conclusion: Whole exome sequence information combined with patient medical record data is allowing Geisinger researchers and research partners to investigate new approaches to prevention, diagnosis and treatment of disease. Strong community engagement programs maintain trust in the system, keep participants engaged in research and continue to guide the evolution of the MyCode program

Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes

Angiopoietin-like 4 (ANGPTL4) is an endogenous inhibitor of lipoprotein lipase that modulates lipid levels, coronary atherosclerosis risk, and nutrient partitioning. We hypothesize that loss of ANGPTL4 function might improve glucose homeostasis and decrease risk of type 2 diabetes (T2D). We investigate protein-altering variants in ANGPTL4 among 58,124 participants in the DiscovEHR human genetics study, with follow-up studies in 82,766 T2D cases and 498,761 controls. Carriers of p.E40K, a variant that abolishes ANGPTL4 ability to inhibit lipoprotein lipase, have lower odds of T2D (odds ratio 0.89, 95% confidence interval 0.85-0.92, p = 6.3 x 10(-10)), lower fasting glucose, and greater insulin sensitivity. Predicted loss-of-function variants are associated with lower odds of T2D among 32,015 cases and 84,006 controls (odds ratio 0.71, 95% confidence interval 0.49-0.99, p = 0.041). Functional studies in Angptl4-deficient mice confirm improved insulin sensitivity and glucose homeostasis. In conclusion, genetic inactivation of ANGPTL4 is associated with improved glucose homeostasis and reduced risk of T2D.Peer reviewe

Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes

Angiopoietin-like 4 (ANGPTL4) is an endogenous inhibitor of lipoprotein lipase that modulates lipid levels, coronary atherosclerosis risk, and nutrient partitioning. We hypothesize that loss of ANGPTL4 function might improve glucose homeostasis and decrease risk of type 2 diabetes (T2D). We investigate protein-altering variants in ANGPTL4 among 58,124 participants in the DiscovEHR human genetics study, with follow-up studies in 82,766 T2D cases and 498,761 controls. Carriers of p.E40K, a variant that abolishes ANGPTL4 ability to inhibit lipoprotein lipase, have lower odds of T2D (odds ratio 0.89, 95% confidence interval 0.85–0.92, p = 6.3 × 10−10), lower fasting glucose, and greater insulin sensitivity. Predicted loss-of-function variants are associated with lower odds of T2D among 32,015 cases and 84,006 controls (odds ratio 0.71, 95% confidence interval 0.49–0.99, p = 0.041). Functional studies in Angptl4-deficient mice confirm improved insulin sensitivity and glucose homeostasis. In conclusion, genetic inactivation of ANGPTL4 is associated with improved glucose homeostasis and reduced risk of T2D

Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes

Angiopoietin-like 4 (ANGPTL4) is an endogenous inhibitor of lipoprotein lipase that modulates lipid levels, coronary atherosclerosis risk, and nutrient partitioning. We hypothesize that loss of ANGPTL4 function might improve glucose homeostasis and decrease risk of type 2 diabetes (T2D). We investigate protein-altering variants in ANGPTL4 among 58,124 participants in the DiscovEHR human genetics study, with follow-up studies in 82,766 T2D cases and 498,761 controls. Carriers of p.E40K, a variant that abolishes ANGPTL4 ability to inhibit lipoprotein lipase, have lower odds of T2D (odds ratio 0.89, 95% confidence interval 0.85–0.92, p = 6.3 × 10−10), lower fasting glucose, and greater insulin sensitivity. Predicted loss-of-function variants are associated with lower odds of T2D among 32,015 cases and 84,006 controls (odds ratio 0.71, 95% confidence interval 0.49–0.99, p = 0.041). Functional studies in Angptl4-deficient mice confirm improved insulin sensitivity and glucose homeostasis. In conclusion, genetic inactivation of ANGPTL4 is associated with improved glucose homeostasis and reduced risk of T2D