️ Episode 79: Cross-Population GWAS and Proteomic Insights in Atrial Fibrillation

In this episode of PaperCast Base by Base, we explore a cross-population genome-wide meta-analysis combined with proteomic profiling to enhance risk prediction and uncover molecular mechanisms underlying atrial fibrillation.

Study Highlights:

The authors conducted a meta-analysis of over 168,000 atrial fibrillation cases across diverse ancestries and identified 525 genome-wide significant loci. They integrated genomic data with large-scale proteomic profiling to discover 28 circulating proteins with potential causal roles in atrial fibrillation. Mendelian randomization analyses highlighted modifiable risk factors such as obesity and hypertension and revealed novel protein targets for therapeutic development. A combined polygenic risk score and protein score significantly improved prediction accuracy for atrial fibrillation beyond existing models. Population-specific analyses uncovered both shared and unique genetic correlations with circulatory comorbidities across European and African ancestries.

Conclusion:

This study demonstrates the power of integrating cross-population genomic and proteomic data to refine atrial fibrillation risk stratification and identify novel therapeutic avenues.

Reference:

Yuan S, Chen J, Ruan X, Li Y, Abramowitz SA, Wang L, Jiang F, Xiong Y, Levin MG, Voight BF, Gill D, Burgess S, Åkesson A, Michaëlsson K, Li X, Damrauer SM & Larsson SC. Cross-population GWAS and proteomics improve risk prediction and reveal mechanisms in atrial fibrillation. Nat Commun. 2025;16:6426. doi:10.1038/s41467-025-61720-2

License:

This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics.