This week on The Genetics Podcast, Patrick is joined by Dr. Pradeep Natarajan, Director of Preventive Cardiology at Massachusetts General Hospital and Associate Professor of Medicine at Harvard Medical School. They discuss the discovery of clonal hematopoiesis as a driver of cardiovascular disease, the inflammatory mechanisms and emerging therapies targeting it, the growing clinical case for polygenic risk scores, and Pradeep's upcoming move to lead cardiometabolic and human genetics research at Amgen.
Show Notes
0:00 Intro to The Genetics Podcast
00:59 Welcome to Pradeep
01:30 The origin story of clonal hematopoiesis (CH) as a cardiovascular risk factor
09:41 CH mutations such as TET2 that are linked to cardiovascular disease
12:27 Evidence tying inflammation to CH and drugs that could target it
16:49 TenSixteen Bio’s strategy for targeting CH and the challenge of finding the right patients
21:33 Trajectory of CH across age and somatic mosaicism beyond blood
26:44 How polygenic risk scores fill a gap in cardiovascular risk prediction
34:49 The future clinical applications of polygenic risk scores
39:20 The challenge of standardizing polygenic risk scores for clinical and regulatory use
42:27 Pradeep's move to pharmaceutical company Amgen and his reasons for it
46:23 Closing remarks
Find out more:
Clonal hematopoiesis paper