EP 248: The blood mutations rewriting cardiovascular risk: Clonal hematopoiesis and polygenic risk with Pradeep Natarajan of Massachusetts General Hospital

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