Pulse Brain · Growing Health Evidence Index
Tier 3 — Observational / field trialPeer-reviewed

Genome-wide association study reveals mechanisms underlying dilated cardiomyopathy and myocardial resilience

Sean J. Jurgens, Joel Rämö, Daria R. Kramarenko, Leonoor F. J. M. Wijdeveld, Jan Haas, Mark Chaffin, Sophie Garnier, Liam Gaziano, Lu‐Chen Weng, Alex Lipov, Sean L. Zheng, Albert Henry, Jennifer E. Huffman, Saketh Challa, Frank Rühle, Carmen Diaz Verdugo, Christian Krijger Juárez, Shinwan Kany, Constance A. van Orsouw, Kiran J. Biddinger, Edwin Poel, Amanda L. Elliott, Xin Wang, Catherine Francis, Richard Ruan, Satoshi Koyama, Leander Beekman, Dominic S. Zimmerman, Jean‐François Deleuze, Eric Villard, David‐Alexandre Trégouët, Richard Isnard, FinnGen, VA Million Veteran Program, D.I. Boomsma, Eco J. C. de Geus, Rafik Tadros, Yigal M. Pinto, Arthur A.M. Wilde, Jouke‐Jan Hottenga, Juha Sinisalo, Teemu Niiranen, Roddy Walsh, Amand F. Schmidt, Seung Hoan Choi, Kyong‐Mi Chang, Philip S. Tsao, Paul M. Matthews, James S. Ware, R Thomas Lumbers, Saskia van der Crabben, Jari A. Laukkanen, Aarno Palotie, Ahmad S. Amin, Philippe Charron, Benjamin Meder, Patrick T. Ellinor, Mark J. Daly, Krishna G. Aragam, Connie R. Bezzina

Nature Genetics · 2024

Read source ↗ All evidence

Summary

This large-scale genome-wide association study identified 70 genetic loci and 63 prioritised genes associated with dilated cardiomyopathy, with strong replication across independent samples. Tissue enrichment analyses emphasised the central role of cardiomyocytes and contractile apparatus in disease pathogenesis. Mendelian randomisation provided evidence for modifiable risk factors—specifically higher bodyweight and elevated systolic blood pressure—suggesting potential targets for preventive intervention.

UK applicability

These findings are applicable to UK clinical genetics and cardiology practice, informing genetic risk stratification and potentially guiding primary prevention strategies targeting bodyweight and blood pressure management in at-risk populations. The polygenic risk score may be integrated into NHS genomic medicine frameworks, though ancestry-specific validation in UK populations would strengthen clinical utility.

Key measures

Genome-wide significant loci; polygenic risk scores; tissue and cell-type enrichment; systolic heart failure association; Mendelian randomisation estimates for bodyweight and blood pressure

Outcomes reported

The study identified 70 genome-wide significant loci associated with dilated cardiomyopathy (DCM) across 9,365 cases and 946,368 controls, mapping to 63 prioritised genes. Polygenic risk scores were constructed and validated across ancestry groups, and Mendelian randomisation identified actionable risk factors including higher bodyweight and systolic blood pressure.

Theme
Nutrition & health
Subject
Dietary patterns & chronic disease
Study type
Research
Study design
Genome-wide association study with multitrait analysis and Mendelian randomisation
Source type
Peer-reviewed study
Status
Published
Geography
International
System type
Human clinical
DOI
10.1038/s41588-024-01975-5
Catalogue ID
SNmoj448pl-zn46gq

Topic tags

Pulse AI · ask about this record

Dig deeper with Pulse AI.

Pulse AI has read the whole catalogue. Ask about this record, its theme, or how the findings apply to UK farming and policy — every answer cites the underlying studies.