| Title: |
Genome-wide analysis of heart failure yields insights into disease heterogeneity and enables prognostic prediction in the Japanese population |
| Authors: |
Nobuyuki Enzan; Kazuo Miyazawa; Satoshi Koyama; Ryo Kurosawa; Hirotaka Ieki; Hiroki Yoshida; Fumie Takechi; Masashi Fukuyama; Ryosuke Osako; Kohei Tomizuka; Xiaoxi Liu; Kouichi Ozaki; Yoshihiro Onouchi; the BioBank Japan Project; Koichi Matsuda; Yukihide Momozawa; Hiroyuki Aburatani; Yoichiro Kamatani; Takanori Yamaguchi; Hiroshi Akazawa; Koichi Node; Patrick T. Ellinor; Michael G. Levin; Scott M. Damrauer; Benjamin F. Voight; Jacob Joseph; Yan V. Sun; Chikashi Terao; Toshiharu Ninomiya; Issei Komuro; Kaoru Ito |
| Source: |
Nature Communications, Vol 16, Iss 1, Pp 1-16 (2025) |
| Publisher Information: |
Nature Portfolio |
| Publication Year: |
2025 |
| Collection: |
Directory of Open Access Journals: DOAJ Articles |
| Subject Terms: |
Science |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doi.org/10.1038/s41467-025-64659-6; https://doaj.org/toc/2041-1723; https://doaj.org/article/995b24e4e2c74e07bfa275a68cd3a887 |
| DOI: |
10.1038/s41467-025-64659-6 |
| Availability: |
https://doi.org/10.1038/s41467-025-64659-6; https://doaj.org/article/995b24e4e2c74e07bfa275a68cd3a887 |
| Accession Number: |
edsbas.CE06DBDC |
| Database: |
BASE |