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Common Variants on FGD5 Increase Hazard of Mortality or Rehospitalization in Patients With Heart Failure From the ASCEND-HF Trial.
- Source :
- Circulation: Heart Failure; Sep2023, Vol. 16 Issue 9, p776-786, 11p
- Publication Year :
- 2023
-
Abstract
- BACKGROUND: Heart failure remains a global health burden, and patients hospitalized are particularly at risk, but genetic associates for subsequent death or rehospitalization are still lacking. METHODS: The genetic substudy of the ASCEND-HF trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) was used to perform genome-wide association study and transethnic meta-analysis. The overall trial included the patients of self-reported European ancestry (n=2173) and African ancestry (n=507). The end point was death or heart failure rehospitalization within 180 days. Cox models adjusted for 11 a priori predictors of rehospitalization and 5 genetic principal components were used to test the association between single-nucleotide polymorphisms and outcome. Summary statistics from the 2 populations were combined via meta-analysis with the significance threshold considered P<5×10-8. RESULTS: Common variants (rs2342882 and rs35850039 in complete linkage disequilibrium) located in FGD5 were significantly associated with the primary outcome in both ancestry groups (European Americans: hazard ratio [HR], 1.38; P=2.42×10-6; African ancestry: HR, 1.51; P=4.43×10-3; HR in meta-analysis, 1.41; P=4.25×10-8). FGD5 encodes a regulator of VEGF (vascular endothelial growth factor)-mediated angiogenesis, and in silico investigation revealed several previous genome-wide association study hits in this gene, among which rs748431 was associated with our outcome (HR, 1.20; meta P<0.01). Sensitivity analysis proved FGD5 common variants survival association did not appear to operate via coronary artery disease or nesiritide treatment (P>0.05); and the signal was still significant when changing the censoring time from 180 to 30 days (HR, 1.39; P=1.59×10-5). CONCLUSIONS: In this multiethnic genome-wide association study of ASCEND-HF, single-nucleotide polymorphisms in FGD5 were associated with increased risk of death or rehospitalization. Additional investigation is required to examine biological mechanisms and whether FGD5 could be a therapeutic target. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 19413289
- Volume :
- 16
- Issue :
- 9
- Database :
- Supplemental Index
- Journal :
- Circulation: Heart Failure
- Publication Type :
- Academic Journal
- Accession number :
- 172339245
- Full Text :
- https://doi.org/10.1161/CIRCHEARTFAILURE.122.010438