Genome-wide analysis of heart failure yields insights into disease heterogeneity and enables prognostic prediction in the Japanese population.
| Authors | |
| Abstract | To understand the genetic basis of heart failure (HF) in the Japanese population, we performed genome-wide association studies (GWASs) comprising 16,251 all-cause HF cases, 4254 HF with reduced ejection fraction (HFrEF) cases, 7154 HF with preserved ejection fraction cases, and 11,122 non-ischemic HF cases among 213,828 individuals and identified five novel loci. A subsequent cross-ancestry meta-analysis and multi-trait analysis of the GWAS data identified 19 novel loci in total, with 31 out of the 76 genome-wide significant loci associated with HFrEF despite its smaller sample size. Among these susceptibility loci, a common non-coding variant in TTN (rs1484116) was associated with reduced cardiac function and worse long-term mortality. We leveraged the HF meta-GWASs along with cardiac function-related GWASs to develop a polygenic risk score (PRS) for HF. The PRS successfully identified early-onset HF and those with an increased risk of long-term HF mortality. Our results shed light on the shared and distinct genetic basis of HF between Japanese and European populations and improve the clinical value of HF genetics.  | 
              
| Year of Publication | 2025 
      
   | 
              
| Journal | Nature communications 
      
   | 
              
| Volume | 16 
      
   | 
              
| Issue | 1 
      
   | 
              
| Pages | 9680 
      
   | 
              
| Date Published | 11/2025 
      
   | 
              
| ISSN | 2041-1723 
      
   | 
              
| DOI | 10.1038/s41467-025-64659-6 
      
   | 
              
| PubMed ID | 41184235 
      
   | 
              
| Links |