Identification of potential therapeutic targets for nonischemic cardiomyopathy in European ancestry: an integrated multiomics analysis
Authors' conclusion
Based on European Ancestry Cohort, this study reveals that LILRA5 and NELL1 are potential therapeutic targets for NISCM, with LILRA5 showing particularly promising prospects in diabetic cardiomyopathy. Several small molecules interact with LILRA5, implying potential clinical implication.
Study context
- Population
- European ancestry: cis-pQTLs from deCODE (35,559 Icelanders); Nonischemic cardiomyopathy (NISCM) GWAS from FinnGen (1,754 NISCM cases, 340,815 controls of Finnish ancestry)
- Outcome
- Causal relationship between circulating plasma protein levels and NISCM risk
Methodological detailscis-pQTL Mendelian randomization, false discovery rate (FDR) correction, Bayesian colocalization, molecular docking
- cis-pQTL Mendelian randomization
- FDR correction
- Bayesian colocalization
- Molecular docking
Main finding
As reported in the abstract
Plasma proteins associated with NISCM (mendelian randomization (MR))
255
Significant after FDR correction
16
LILRA5, protective effect: OR
0.758 (0.670-0.857) (95% CI)
NELL1, risk effect: OR
1.290 (1.199-1.387) (95% CI)
Further findings
Tissue expression in NISCM datasets
- Decreased LILRA5 expression in diabetic, hypertrophic, dilated and inflammatory cardiomyopathy; NELL1 expression increased in hypertrophic cardiomyopathy
- Human Protein Atlas (HPA): high LILRA5 expression in neutrophils, macrophages and endothelial cells in normal heart; limited NELL1 expression
- Immune infiltration: decreased neutrophils in diabetic cardiomyopathy
Small molecules interacting with LILRA5 (Comparative Toxicogenomics Database (CTD), molecular docking)
- Estradiol, Estradiol-3-benzoate, Gadodiamide, Topotecan and Testosterone stably bind LILRA5 at conserved VAL-15 or THR-133 residues in the Ig-like C2 domain
Original publication
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