What is the clinical evidence from this study?

Study design: Observational. Population: Hypertrophic cardiomyopathy (n=337159). Intervention: Genetically predicted TNNT1 expression vs. Control. Primary outcome: Risk of hypertrophic cardiomyopathy (OR 1.0001, 95% CI 1.0000-1.0003, p=0.033).

What question did this study set out to answer?

To identify genetic factors contributing to the pathogenesis of hypertrophic cardiomyopathy (HCM) through integrated analysis.

April 30, 2026Journal of Cardiothoracic Surgery0 citationsOpen Access

A new insight of hypertrophic cardiomyopathy: integrated analysis of differentially expressed genes, expression quantitative trait loci, and mendelian randomization

YGYaozong Guan HWHuai Wang HHHuanjie Huang

Key Result

Genetically predicted TNNT1 expression was identified as a risk factor (OR 1.0001) and CXCL6 as a protective factor (OR 0.9996) for hypertrophic cardiomyopathy.

Key Points

To identify genetic factors contributing to the pathogenesis of hypertrophic cardiomyopathy (HCM) through integrated analysis.
Used microarray datasets from three independent HCM sources for analysis.
Conducted differential expression analysis, eQTL analysis, and Two-Sample Mendelian Randomization (TSMR) for gene identification.
Applied CIBERSORT for assessing immune cell infiltration and performed molecular docking for drug binding assessment.
Identified four co-expressed genes (TNNT1, KCNK17, GADD45B, CXCL6) significantly enriched in key biological pathways related to HCM.
Validated TNNT1 and CXCL6 as novel genetic targets, strengthening the findings' reliability.
Predicted candidate compounds (Atorvastatin, Zearalenone, Cotinine, S-1,2-Dichlorovinyl-N-acetylcysteine) with evaluated binding affinity to the identified proteins.

Study Design

Type

Observational (n=337,159)

Structured PICO

Population

Three independent microarray datasets of Hypertrophic cardiomyopathy (HCM) and controls

Intervention

Integrated analysis of differentially expressed genes (DEGs), expression quantitative trait loci (eQTL), Two-Sample Mendelian Randomization (TSMR), and molecular docking

Comparator

Control samples

Outcome

Identification of novel genetic targets and candidate compounds for HCMsurrogate

Integrated bioinformatics analysis identified TNNT1 and CXCL6 as novel candidate genetic targets for hypertrophic cardiomyopathy.

Main Result

Effect estimate: OR 1.0001 (95% CI 1.0000-1.0003)

p-value: p=0.033

Abstract

Hypertrophic cardiomyopathy (HCM) has a genetic basis, with pathogenic variants identified in the majority of familial cases and unclear mechanism. This study aimed to identify the genetic contributors underlying HCM pathogenesis and to identify novel genetic targets of HCM via integrated analysis of microarray datasets. Three independent HCM datasets were used for comprehensive analysis by using R software. Differentially expressed genes (DEGs) between HCM and control, expression quantitative trait loci (eQTL) analysis, and Two-Sample Mendelian Randomization (TSMR) analyses were performed to identify the novel genes. CIBERSORT was utilized for immune cell infiltration analysis. Finally, the identified genes were verified, and their targeted drugs were explored. TSMR analysis revealed that four significantly HCM co-expressed genes, TNNT1 , KCNK17 , GADD45B , and CXCL6 , were enriched in essential biological processes and pathways, including macrophage activation and neural system regulation. TNNT1 and CXCL6 genes were validated as the novel genes, enhancing the reliability of our findings. The candidate compounds with predicted binding affinity (Atorvastatin, Zearalenone, Cotinine, and S-1,2-Dichlorovinyl-N-acetylcysteine) were predicted and molecular docking was performed to evaluate the binding ability of the drug to the protein. This study reveals a new molecular insight in the pathogenesis of HCM, highlighting TNNT1 and CXCL6 as candidate targets in specific molecular pathways for the interference of HCM.

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