Abstract 4361108: Genome-wide analysis of heart failure yields insights into disease heterogeneity and enables prognostic prediction in the Japanese population
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, 4,254 HF with reduced ejection fraction cases, 7,154 HF with preserved ejection fraction cases, and 11,122 non-ischemic HF cases among 213,828 individuals (Figure 1) and identified five novel loci (Figure 2). A subsequent cross-ancestry meta-analysis and multi-trait analysis of the GWAS data identified 19 novel loci in total. 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 (Figure 3). 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.
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Authors (29)
Nobuyuki Enzan
Kazuo Miyazawa
Satoshi Koyama
Ryo Kurosawa
Hirotaka Ieki
Fumie Takechi
Masashi Fukuyama
Ryosuke Osako
Kohei Tomizuka
Xiaoxi Liu
Kouichi Ozaki
Yoshihiro Onouchi
Koichi Matsuda
Yukihide Momozawa
Hiroyuki Aburatani
Yoichiro Kamatani
Takanori Yamaguchi
Hiroshi Akazawa
Koichi Node
Patrick Ellinor
The Broad Institute, Cambridge, Massachusetts, United States
Michael Levin
Scott Damrauer
Benjamin Voight
UNIVERSITY OF PENNSYLVANIA, Philadelphia, Pennsylvania, United States
Jacob Joseph
Yan Sun
Chikashi Terao
Toshiharu Ninomiya
Issei Komuro
Kaoru Ito