Krishna Aragam: Why are (DCM) and Heart Failure About Twice as Common in Individuals of Self-Identified Black Race?
Krishna Aragam, Director of Cardiovascular Genomics at Cleveland Clinic, posted on LinkedIn:
“Why are dilated cardiomyopathy (DCM) and heart failure about twice as common in individuals of self-identified Black race?
This risk difference has long been recognized but not fully explained by traditional risk factors or social determinants.
Our new paper in Nature Genetics identifies a key contributor: **a common loss-of-function variant in the gene CD36, specific to individuals of African ancestry, that increases risk of DCM.**
In the VA Million Veteran Program, we found that:
• 1 in 6 of African ancestry carries one copy → ~33% higher DCM risk
• 1 in 100 of African ancestry carries two copies → ~3× higher risk
• Variant is virtually absent in other populations
This single CD36 variant explains 8% of DCM in African ancestry populations — a greater impact on DCM than diabetes or chronic kidney disease — and accounts for 20% of the excess DCM risk compared with European ancestry individuals.
Mechanistically, CD36 encodes the transporter responsible for moving long-chain fatty acids (the heart’s main fuel) into cardiomyocytes. We found that loss of CD36 impairs fuel uptake, mitochondrial energy production, and contractility — revealing a myocardial energetic pathway to heart failure.
The variant’s higher frequency likely reflects positive selection in sub-Saharan Africa, where CD36 deficiency may have conferred protection against severe malaria.
This represents a new paradigm linking ancestry, metabolism, and heart failure.
Grateful to an extraordinary team across institutions, especially Jennifer Huffman, Liam Gaziano, and Zeina Al Sayed for leading this work, and Patrick Ellinor, Jacob Joseph, and Yan Sun for key support.
And most importantly, to all Veterans in the U.S. Department of Veterans Affairs Million Veteran Program, without whom this discovery would not have been possible.
Looking forward to extending this work across Cleveland Clinic, Mass General Brigham, the Broad Institute of MIT and Harvard, and other collaborating institutions to better understand the biology, refine early risk prediction, and explore how insights into myocardial energetics may guide new strategies for heart failure prevention and therapy.”
Title: An African ancestry-specific nonsense variant in CD36 is associated with a higher risk of dilated cardiomyopathy
Authors: Jennifer E. Huffman, Liam Gaziano, Zeina R. Al Sayed, Renae L. Judy, Laura M. Raffield, Kiran J. Biddinger, Brian Charest, Anant Chopra, David Gagnon, Xiuqing Guo, Vera Koledova, Michael G. Levin, Yuan-I Min, James P. Pirruccello, Nosheen Reza, Richard Ruan, Shefali Setia Verma, Bharath Ambale Venkatesh, Anurag Verma, Jie Yao, John Jeffrey Carr, Juan P. Casas, Kelly Cho, Joao A. C. Lima, Wendy S. Post, Daniel J. Rader, Marylyn D. Ritchie, Amil Shah, Kent D. Taylor, James G. Terry, Stephen S. Rich, Christopher J. O’Donnell, Lawrence S. Phillips, Kathryn L. Lunetta, Jerome I. Rotter, Peter W. F. Wilson, J. Michael Gaziano, Scott M. Damrauer, Yan V. Sun, Patrick T. Ellinor, Jacob Joseph, Krishna G. Aragam
Read full paper here.
Stay informed with Hemostasis Today.
-
Nov 2, 2025, 14:172019 ESC/EAS Guidelines for the Management of Dyslipidaemias Discussion with Lale Tokgözoğlu and Jeanine Roeters van Lennep
-
Nov 2, 2025, 14:14Nihar Desai: Post-Transplant Dysphagia
-
Nov 2, 2025, 14:13Zia Choudhry Launchs a New Digital Education Platform Designed to Inform and Empower People Living With wAIHA
-
Nov 2, 2025, 14:13Rahul Bhargava: Landmark Study Shows Excellent Outcomes in Pediatric AML Transplant
-
Nov 2, 2025, 10:17ESO: Register for the Live WSC 2025 Highlights Webinar
-
Nov 2, 2025, 14:21Claude Franceschi: I Advise You to Understand the Hemodynamic Pathophysiology of Venous Diseases Rather than Blindly Applying Ablation Techniques or Venous Stent Placement
-
Nov 2, 2025, 14:15Krishna Aragam: Why are (DCM) and Heart Failure About Twice as Common in Individuals of Self-Identified Black Race?
-
Nov 2, 2025, 14:15Raul Santos: Waist-to-Height Ratio and Coronary Artery Calcium Incidence
-
Nov 2, 2025, 14:12Steven AR Murphy: Urolithin A Shows Immune Rejuvenation and Mitochondrial Benefits in New Trial
-
Nov 2, 2025, 10:31Cihan Ay and RIETE Investigators Team Present External Validation of the VTE-PREDICT Score
-
Oct 29, 2025, 07:31The Use of Artificial Intelligence to Improve Detection of Acute Incidental Pulmonary Emboli - JTH
-
Oct 29, 2025, 07:05Shrinidhi Nathany: AI in Diagnostic Medicine
-
Oct 28, 2025, 07:02Aya Berman: AI Model for Predicting Bacteremia
-
Oct 28, 2025, 06:55The New Era of Genomics, AI and Cell Therapy in Hematology and Infectious Diseases
-
Oct 28, 2025, 06:49Lukas Gaats: Researchers Are Building Reproductive Organoids
-
Nov 2, 2025, 14:17Anamaria B: Your Mother Still Runs Part of Your DNA
-
Nov 2, 2025, 10:57Paul Bolaji on Launching The First Centralised Nigerian National Stroke Registry
-
Nov 2, 2025, 10:03Mark Stoffels: A Stroke Can Change Lives in an Instant, But With Timely Expert Care Recovery is Possible
-
Nov 2, 2025, 09:43Louise Bannon Celebrates Barbara Adams Krolak’s 10-Year Anniversary at ISTH
-
Nov 2, 2025, 08:06Sanam Loghavi Recognized at Inaugural Women in Hematology U.S. Focus Meeting 2025