What question did this study set out to answer?

Characterize cardiomyopathy-associated genes harboring rare variants of uncertain significance and uncover their cellular contexts using single-cell transcriptomics.

January 10, 2026Scientific ReportsOpen Access

Unraveling the cellular characteristics of cardiomyopathy with rare variant-driven gene signatures using multi-omics analysis

Q: What are the key findings of this study?

Burden analysis identified 144 gene signatures enriched in pathways related to cardiac tissue development, correlated with cardiomyopathy phenotypes in 245 patients.

Q: What does this research mean for the field?

Burden analysis identified 144 gene signatures enriched in pathways related to cardiac tissue development, correlated with cardiomyopathy phenotypes in 245 patients. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

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Key result

Genomic burden analysis links 144 cardiac tissue development gene signatures to cardiomyopathy phenotypes.

Why the study?

Advances in whole-genome sequencing have led to an increase in uncharacterized variants with unknown functions, prompting efforts to characterize cardiomyopathy-associated genes with rare variants and uncover their cellular contexts.

Key Points

Characterize cardiomyopathy-associated genes harboring rare variants of uncertain significance and uncover their cellular contexts using single-cell transcriptomics.
Analyzed whole-genome sequencing data from 245 unrelated Korean patients with dilated (48.2%) or hypertrophic (47.8%) cardiomyopathy.
Performed gene-level burden testing with the SKAT-O test on 3,534 variants of uncertain significance to identify enriched candidate genes and pathways.
Profiled single-cell transcriptomes across 11,664 heart tissue cells from an independent cohort (6 patients with heart disease and 14 healthy controls) to assess cell heterogeneity.
Identified 3,584 rare variants across the cohort, including 50 pathogenic or likely pathogenic variants in 41 patients and 3,534 variants of uncertain significance.
Detected 144 significant burden genes via SKAT-O (P < 0.05), which were enriched in cardiac muscle tissue development, heart morphogenesis, and endocrine system development (FDR < 0.003).
Characterized five major cardiac cell types from 11,664 cells, demonstrating cellular heterogeneity and dynamic interactions between cardiomyocytes and endothelial cells.

Structured PICO

Population

245 unrelated Korean patients with cardiomyopathy (48.2% dilated cardiomyopathy, 47.8% hypertrophic cardiomyopathy, 4.1% others), 71.8% male. The study also utilized single-cell RNA-sequencing data from 11,664 heart tissue cells (6 heart disease patients, 14 healthy controls) and bulk RNA-seq data from 194 cardiomyopathy patients and 166 healthy individuals.

Intervention

Whole-genome sequencing (WGS) and single-cell RNA-sequencing (scRNA-seq) to identify rare variant-driven gene signatures and their cellular contexts.

Comparator

Healthy controls (for transcriptomic analyses).

Outcome

Identification of rare variants, burden analysis of variants of uncertain significance (VUS), and cellular context of gene signatures.surrogate

Multi-omics analysis of cardiomyopathy patients reveals that rare variants of uncertain significance are significantly enriched in cardiac development pathways and exhibit cell-type specific expression in both cardiomyocytes and endothelial cells.

Discussion

No takes yet. Share an insight, caveat, or question.

Implication

Hypothesis-generating for rare variant roles in cardiomyopathy; leaves open clinical utility pending larger validation studies.

Cite This Study

Jeong et al. (2025) studied this question. Burden analysis identified 144 gene signatures enriched in pathways related to cardiac tissue development, correlated with cardiomyopathy phenotypes in 245 patients.

synapsesocial.com/papers/6963220c91e05aa366cb87ba https://doi.org/10.1038/s41598-025-33901-y

Topics

Cardiomyopathy

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Unraveling the cellular characteristics of cardiomyopathy with rare variant-driven gene signatures using multi-omics analysis

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Topics

Unraveling the cellular characteristics of cardiomyopathy with rare variant-driven gene signatures using multi-omics analysis

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Also Consider

Topics

Also Consider