Dataset Information

Exploring Key Genes to Construct a Diagnosis Model of Dilated Cardiomyopathy.

ABSTRACT:

Background

Dilated cardiomyopathy (DCM) is characterized by left ventricular dilatation and systolic dysfunction. The pathogenesis and etiologies of DCM remain elusive. This study aims to identify the key genes to construct a genetic diagnosis model of DCM.

Methods

A total of 257 DCM samples from five independent cohorts were enrolled. The Weighted Gene Co-Expression Network Analysis (WGCNA) was performed to identify the key modules associated with DCM. The latent mechanisms and protein-protein interaction network underlying the key modules were further revealed. Subsequently, we developed and validated a LASSO diagnostic model in five independent cohorts.

Results

Two key modules were identified using WGCNA. Novel mechanisms related to the extracellular, mitochondrial matrix or IL-17 signaling pathway were pinpointed, which might significantly influence DCM. Besides, 23 key genes were screened out by combining WGCNA and differential expression analysis. Based on the key genes, a genetic diagnosis model was constructed and validated using five cohorts with excellent AUCs (0.975, 0.954, 0.722, 0.850, 0.988). Finally, significant differences in immune infiltration were observed between the two groups divided by the diagnostic model.

Conclusion

Our study revealed several novel pathways and key genes to provide potential targets and biomarkers for DCM treatment. A key genes' diagnosis model was built to offer a new tool for diagnosing DCM.

SUBMITTER: Zheng Y

PROVIDER: S-EPMC9091505 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Exploring Key Genes to Construct a Diagnosis Model of Dilated Cardiomyopathy.

Zheng Youyang Y Liu Zaoqu Z Yang Xinyue X Weng Siyuan S Xu Hui H Guo Chunguang C Xing Zhe Z Liu Long L Wang Libo L Dang Qin Q Qiu Chunguang C

Frontiers in cardiovascular medicine 20220427

<h4>Background</h4>Dilated cardiomyopathy (DCM) is characterized by left ventricular dilatation and systolic dysfunction. The pathogenesis and etiologies of DCM remain elusive. This study aims to identify the key genes to construct a genetic diagnosis model of DCM.<h4>Methods</h4>A total of 257 DCM samples from five independent cohorts were enrolled. The Weighted Gene Co-Expression Network Analysis (WGCNA) was performed to identify the key modules associated with DCM. The latent mechanisms and p ...[more]

PMID: 35571180

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Project description:BackgroundObservational clinical studies suggest an association between dilated cardiomyopathy (DCM) and various factors including titin, cardiac troponin I (CTnI), desmocollin-2, the perinatal period, alcoholism, Behçet's disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, and renal insufficiency. The causal nature of these associations remains uncertain. This study aims to explore these correlations using the Mendelian randomization (MR) approach.ObjectiveTo investigate the etiology of DCM through Mendelian randomization analysis.MethodsData mining was conducted in genome-wide association study databases, focusing on variant target proteins (titin, CTnI, desmocollin-2), the perinatal period, alcoholism, Behçet's disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, and renal insufficiency, with DCM as the outcome. The analysis employed various regression models, namely, the inverse-variance weighted (IVW), MR-Egger, simple mode, weighted median, and weighted mode methods.ResultsThe IVW results showed a correlation between titin protein and DCM, identifying titin as a protective factor [OR = 0.856, 95% CI (0.744-0.985), P = 0.030]. CTnI protein correlated with DCM, marking it as a risk factor [OR = 1.204, 95% CI (1.010-1.436), P = 0.040]. Desmocollin-2 also correlated with DCM and was recognized as a risk factor [OR = 1.309, 95% CI (1.085-1.579), P = 0.005]. However, no causal relationship was found between the perinatal period, alcoholism, Behçet's disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, renal insufficiency, and DCM (P > 0.05). The MR-Egger intercept test indicated no pleiotropy (P > 0.05), affirming the effectiveness of Mendelian randomization in causal inference.ConclusionTitin, CTnI, and desmocollin-2 proteins were identified as independent risk factors for DCM. Contrasting with previous observational studies, no causal relationship was observed between DCM and the perinatal period, alcoholism, Behçet's disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, or renal insufficiency.

Dataset Information

Exploring Key Genes to Construct a Diagnosis Model of Dilated Cardiomyopathy.

Background

Methods

Results

Conclusion

Publications

Exploring Key Genes to Construct a Diagnosis Model of Dilated Cardiomyopathy.

Similar Datasets

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