Genomic health sits at the intersection of human genetics, precision medicine, and public health. It requires close collaboration between biologists, clinicians, data scientists, population health specialists as well as many other partners across multiple fields. In order to foster these collaborations, the Yale School of Medicine’s Dean’s Office hosted a workshop to introduce the Yale Center for Genomic Health (YCGH) to the Yale community. It was an event that brought together scholars and professionals from across diverse disciplines to learn more about the science of genomic healthcare and the vision of the YCGH.
Dr. Nancy Brown, Jean and David W. Wallace Dean of the Yale School of Medicine and C.N.H. Long Professor of Internal Medicine opened the event by welcoming everyone to the workshop and explaining the mission of the YCGH. “This was launched last year and brings together researchers and other partners investigating the genetic basis of health and disease”, Brown stated. Following Brown, Dr. Antonio Giraldez, Fergus F. Wallace Professor of Genetics and Chair of the Department of Genetics shared his excitement about the establishment of YCGH. Giraldez said that the YCGH was made possible only through the partnership of the Yale School of Medicine and the Yale New Haven Hospital and the tremendous efforts of its leaders. As genomic sequencing becomes the standard practice for diagnosing patients in the future, Giraldez envisions that the YCGH will be “poised to make many novel discoveries that allow us to interpret the genome and define the mechanisms of disease.” A later address from Dr. Keith Churchwell, President of Yale New Haven Hospital and Associate Clinical Professor of Medicine, underscored the importance of genomic health in clinical care and the strong partnership between Yale New Haven Hospital and Yale School of Medicine.
A key aim of the workshop was to introduce Dr. Ira Hall, Professor of Genetics and inaugural Director of YCGH. Hall, now with almost a year under his belt as Director, formally introduced the center and outlined how its planned activities will move the field of genomic research forward. To demonstrate the rapid progress of genetics research, Hall talked about the ways that high throughput DNA sequencing technologies, developed only in the last decade, have transformed the study of genomes in the lab and clinic. The next step for the field is the application of these technologies to explore and catalog genetic variation across the human population and to use these data to improve healthcare. “There’s a lot to do here,” Hall stated. “The possibilities are immense. I think thirty years from now we’ll look at the moment we’re in as the golden age, the inflection point of what came before and what came after.” On the clinical genetics side, Yale has long played a significant role in the expanding research and care of rare diseases, as noted by Dr. Yong-Hui Jiang, Professor of Genetics and Chief of Medical Genetics in his presentation on the “Genomic Approach of Undiagnosed and Rare Diseases.” Dr. Monkol Lek, Assistant Professor of Genetics, also spoke about how genomic technologies can now transform the rare disease patient journey, from a shorter diagnostic odyssey to the development of targeted therapies.
The workshop also provided a platform to showcase Yale’s Generations project, led by Professor of Genetics Dr. Mike Murray. The Generations project aims to collect DNA samples from volunteers of all ages and health statuses across Connecticut. This DNA biobank will include samples from diverse populations within New Haven, a city that is demographically representative of the U.S. as a whole. As researchers learn more about human health and disease from these large genomic datasets, volunteers and their providers could receive clinical information that improves care and informs medical decisions. Following Murray, Dr. Wade Schulz, Director of Informatics and Assistant Professor and of Laboratory Medicine spoke about the challenges and opportunities in the emerging field of computational health and how big datasets like Generations will be used. Schultz is also Medical Director of Data Science for Yale New Haven Health System and will be working across both Yale New Haven Health and Yale School of Medicine to accelerate data-driven research and health outcomes.
One key goal of the YCGH is to ensure that the next generation of gene discovery projects captures the full diversity of the human race. “We need to make every effort to make sure that we do a better job at including diverse ancestry groups in the studies that we do,” Hall said. “Most of our knowledge has been built upon large studies of European descent individuals. This is a real problem because as this trickles down into the healthcare arena, the algorithms that we use in risk prediction and clinical decision-making are going to be biased.” Many presenters at the event reiterated the field’s responsibility to collect and investigate datasets that reflect the diversity of the human population. Dr. Joel Gelernter, the director of the Division of Human Genetics in Psychiatry, discussed the advantages of the Million Veterans Program biobank for genome-wide associated studies in his presentation “Mapping Risk Genes for Psychiatric Disorders in Large Samples to Understand Biology.” The biobank has a large and growing sample size for investigators to perform meta-analyses to study complex psychiatric traits like post-traumatic stress disorder. Furthermore, unlike most large biobanks, the Million Veterans Program has good representation from African American and Latinx populations, which enhances gene discovery, as Gelernter explained in his talk. Taking a different approach to understand psychiatry, Dr. Kristen Brennand, Professor of Psychiatry is using stem cells to explore the genetics of schizophrenia. She spoke about the complex genetic risk architecture of schizophrenia, stating that “…genetics here is not yet diagnostic. There are strong and significant group differences between patients and controls, but we can’t yet harness the power of all this genetic information to make meaningful insights for our patients.” Her lab is studying risk variants with the goals of improving diagnostics for patients and finding new therapies based on genetic findings.
The YCGH encourages collaborations not just within Yale but also nationwide and internationally. Dr. Martina Brueckner, Professor of Pediatrics (Cardiology) and of Genetics, provided an example of one such collaborative effort. In her presentation, “Genetic Cause and Developmental Mechanisms Underlying Congenital Heart Disease,” Dr. Brueckner discussed the impact of the NIH/NHLBI-funded Pediatric Cardiac Genomics Consortium (PCGC). Involving hospitals across the U.S. and the U.K., the PCGC is currently the largest congenital disease cohort with over 14,000 recruits. The Yale Center for Genome Analysis has long been involved with the project as a genetic sequencing center. Their targeted sequencing technology has allowed the PCGC to expand the cohort size, making genotype-phenotype correlations of congenital heart disease (CHD) possible. The more the PCGC can discover about CHD through genomic analyses, the better the care they can provide to their patients. In other large-scale approaches, Dr. Chris Cotsapas, Associate Professor of Neurology and of Genetics, gave a presentation on “Using Large-Scale Clinical Data for Discovery In Multiple Sclerosis And Epilepsy.” He discussed the challenges of uniting data across global networks of biobanks and the promise in the years ahead for biobanks like MultipleMS that will help researchers better understand different groups of patients with multiple sclerosis. Dr. Morgan Levine, Assistant Professor of Pathology and of Epidemiology (Chronic Diseases), spoke about a systems-level approach to track epigenetic changes of aging. “Aging is the biggest risk factor for most of the chronic diseases that people suffer and die from in the U.S. and worldwide,” Levine says. In her lab’s work to quantify biological aging using epigenetic clocks, they found that biological aging is modifiable, which is foundational to developing new therapeutics and risk stratification models for chronic diseases.
Even with a fully packed schedule of exciting back-to-back presentations, the virtual workshop only scratched the surface of Yale-led genomics research initiatives. In the years to come, YCGH will inspire and facilitate more scientists, clinicians, and interdisciplinary leaders to work together to improve patients’ lives and cure diseases through genomic health. For the full list of presenters and a recording of the presentations, visit the Dean’s Workshops website.