In this episode of Precision Medicine Made Simple, we welcome back Dr. Yelena Bykhovskaya, the Chief Scientific Officer at Biography Health, for a deep dive into polygenic risk scores (PRS) and their emerging role in precision medicine. Dr. Bykhovskaya breaks down the complexities of genetics and its application in clinical practice, focusing on how polygenic risk scores can be used to assess an individual's risk for common complex diseases.

We discuss the evolution of genetics in healthcare, how PRS differs from monogenic testing, and why the accuracy and predictive power of these scores are becoming increasingly important. We also address some of the challenges in applying PRS across different populations and the future potential of genetic risk scores in personalized healthcare.

Key Takeaways:

• Polygenic risk scores are a powerful tool for assessing genetic predisposition to complex diseases like heart disease, Alzheimer’s, and more.
• PRS are calculated using multiple genetic variants, not just one, making them useful in understanding complex traits.
• While still evolving, PRS are becoming more accurate, especially with the incorporation of data from diverse populations.
• Understanding PRS can help prevent diseases before they manifest, offering proactive healthcare solutions.
• The challenges and benefits of integrating PRS into clinical practice, and how the field is rapidly advancing.

In This Episode:

• [00:00] Introduction to polygenic risk scores and their relevance in precision medicine
• [05:00] How the Human Genome Project and next-generation sequencing revolutionized genetics
• [10:00] Explaining the difference between monogenic and polygenic diseases
• [15:00] The limitations of current PRS models and how they’re improving over time
• [20:00] Why PRS is especially useful for assessing cardiovascular risk and other common conditions
• [25:00] The impact of ancestral diversity on PRS and how researchers are making improvements
• [30:00] What it takes for PRS to move from research to clinical use
• [35:00] The potential for PRS to inform more personalized treatment plans
• [40:00] Dr. Bykhovskaya’s personal experience with blood pressure medication and how PRS could have helped
• [45:00] How precision medicine is changing the way we think about healthcare

Notable Quotes:

• “Polygenic risk scores are not just about predicting the future, they’re about empowering people to take control of their health today.” – Dr. Yelena Bykhovskaya
• “You can't just focus on a single gene; it's about the whole picture, understanding how multiple genetic factors contribute to disease risk.” – Dr. Yelena Bykhovskaya
• “Genetics is a moving field, and as we gather more data, the accuracy and usefulness of PRS will continue to improve.” – Dr. Yelena Bykhovskaya
• “Personalized medicine is about understanding you as an individual and tailoring healthcare to your specific needs, not just your symptoms.” – Dr. Yelena Bykhovskaya

Our Guest

Dr. Yelena Bykhovskaya is the Chief Scientific Officer at Biography Health, where she...

In this episode of Precision Medicine Made Simple, we’re joined by Dr. Rich Joseph, a physician with a rare blend of expertise as both a strength and conditioning specialist and a competitive athlete. Dr. Joseph is the founder of VIM Medicine and the Board Chair of Vital Connections. He’s also a faculty member at Harvard Medical School and Brigham and Women’s Hospital, where he focuses on preventive medicine.

Dr. Joseph’s unique approach integrates performance medicine, which he defines as the capacity to bring energy and attention to what matters most in life. His philosophy blends athletic mindset and proactive health practices to help people achieve peak performance in all aspects of life—physical, mental, and emotional.

In this episode, we dive into his journey from athlete to physician, how he started VIM Medicine, and how performance medicine can optimize health and longevity. We also discuss the importance of mindset, recovery, and behavior in achieving long-term wellness.

• The concept of performance medicine and its relevance to overall well-being.
• How performance-based healthcare goes beyond disease treatment to emphasize proactive, personalized care.
• The importance of behavioral grounding and experimentation in health optimization.
• How to use performance metrics like VO2 max and strength to monitor and improve health.
• The evolution of health insurance and its role in a more proactive, patient-centered care model.
• The growing field of longevity and the need for more balance in the conversation around aging

• [00:00] Introduction to Dr. Rich Joseph’s approach to performance medicine
• [05:15] Transitioning from athletic training to a medical career
• [10:00] The importance of a mindset focused on progress over perfection
• [14:30] Starting VIM Medicine and the integration of exercise into healthcare
• [20:00] The role of recovery and mindset in optimizing longevity
• [25:00] Exploring peptides, supplements, and managing the noise in health trends
• [30:00] Biomarkers: What should you focus on for long-term health?
• [35:00] The difference between functional medicine, longevity medicine, and personalized care
• [40:00] Vital Connections and the effort to address healthcare inequities in Boston
• [45:30] Dr. Joseph’s vision for the future of healthcare and his practice’s growth

• “Health is an asset, something you have to strategically manage and invest over the long term.” – Dr. Rich Joseph
• “You can’t just treat the symptoms; you have to optimize performance to live well.” – Dr. Rich Joseph
• “Prevention is not sexy, but performance is something everyone can get behind.” – Dr. Rich Joseph
• “You have to pair stimulus with recovery to create adaptation.” – Dr. Rich Joseph

Dr. Rich Joseph is a Harvard-trained internist, founder of VIM Medicine, and Chief Medical Officer at Restore Hyper Wellness. With a background in strength and conditioning, he has created a unique model of Performance Medicine that combines athletic principles with healthcare. His approach emphasizes proactive health strategies, personalized wellness, and performance optimization. Dr. Joseph also leads Vital Connections, a nonprofit focused on improving health equity and community well-being.

Dr. Rich Joseph

• https://www.linkedin.com/in/rich-joseph-md-mba-61448b33a/

Most of today’s healthcare still treats problems after they happen. Dr. Leroy Hood thinks that needs to change. In this episode of Precision Medicine Made Simple, he explains how genomics, regular health tracking, and AI can shift the focus to preventing disease before it starts.

Dr. Hood is one of the scientists who helped build the automated DNA sequencer that powered the Human Genome Project. He also founded the Institute for Systems Biology. He has worked across research, government, and healthcare to push ideas that were unpopular at the time but are now standard practice.

You’ll hear how he went from a professor at Caltech to building new departments, starting research institutes, and working with governments around the world to change how healthcare works.

He also explains the idea of P4 medicine: predictive, preventive, personalized, and participatory care and why most of the healthcare system isn’t built to support it yet.

• Seven shifts that shaped Dr. Hood’s career and could change medicine
• Why most healthcare money goes to chronic disease and how to cut that
• How genome and phenome data can find diseases years before symptoms
• What polygenic risk scores mean for different ethnic groups
• How AI helps doctors create personalized care plans
• How useful data can slow aging, prevent Alzheimer’s, and support your health
• Why chasing profits slows down U.S. healthcare
• How kids in Seattle learn to manage their own health
• Why commercial insurance may fail if it doesn’t adapt
• How Tom Brady trained his brain to last longer and how you can apply that

• [00:00] Introduction to Dr. Leroy Hood's journey
• [01:49] The evolution of precision medicine
• [03:11] Introducing Dr. Leroy Hood
• [04:41] Dr. Hood's early career and challenges
• [06:43] The birth of systems biology
• [08:20] Pioneering cross-disciplinary research
• [10:56] The Human Genome Project
• [13:49] Establishing systems biomedicine
• [22:51] The Luxembourg initiative
• [23:45] Data-driven health insights
• [30:42] Challenges with polygenic risk scores
• [31:42] Ancestry and genetic variants
• [32:52] Pharmacogenomics and drug response
• [33:16] Rare diseases and carrier status
• [34:57] Lifestyle genetics and athletic injuries
• [36:18] Actionable possibilities in genomics
• [38:27] Economic impact of chronic disease prevention
• [39:04] Obstacles to deep health analysis
• [40:48] Advancements in personalized medicine
• [45:50] The future of health care and AI
• [56:15] Brain health and cognitive function
• [59:39] Conclusion and future topics

• [00:00:39] "I decided “Big Data” was necessary to deconvolute the complexity of human biology. But the instrumentation for “Big Data” didn't exist at that point in time." — Dr. Leroy Hood
• [00:11:41] "The big science of the genome project revolutionized so many fields of biology in profound ways that it's really quite remarkable." — Dr. Leroy Hood
• [00:12:15] "The Human Genome absolutely transformed our understanding of how we can think about human biology." — Dr. Leroy Hood
• [00:13:39] "If you really want to have fun with science, you can't do it at a place where people are criticizing two of the major thrusts in your laboratory." — Dr. Leroy Hood
• [00:44:14] "Over the last 40 years, Americans extended their lifespan by 10 years. They didn't expand their health span by a single year." — Dr. Leroy...