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Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
Mendelian randomization analysis and molecular mechanism study of childhood asthma and obstructive sleep apnea
Xinyu Wang1, Lin Zhang1,2, Hao Chen3
1Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300, Nanjing, 210029, China.
Insights
Childhood asthma and obstructive sleep apnea (OSA) share molecular links. Three hub genes (LRP3, BAK1, CLIC4) are key to immune modulation in both conditions, suggesting new therapeutic targets.
Area of Science:
- Genetics
- Immunology
- Respiratory Medicine
Background:
- Childhood asthma is a prevalent chronic respiratory condition.
- Obstructive sleep apnea (OSA) is an increasingly recognized comorbidity in children with asthma.
- Understanding the molecular links between asthma and OSA is crucial for effective management.
Purpose of the Study:
- To investigate the molecular mechanisms underlying the comorbidity of childhood asthma and OSA.
- To identify shared genetic factors and hub genes connecting these two conditions.
- To explore the role of these genes in immune modulation and potential therapeutic strategies.
Main Methods:
- Mendelian randomization (MR) analysis was employed.
- Publicly available gene expression and genotype data were analyzed.
- Identification of single nucleotide polymorphisms (SNPs) associated with both asthma and OSA.
Main Results:
- 242 gene pairs linked to childhood asthma and 350 to OSA were identified.
- Three hub genes (LRP3, BAK1, CLIC4) showed significant expression changes in both diseases.
- These genes are involved in signal transduction, immune cell infiltration, and the immune microenvironment.
Conclusions:
- A bidirectional molecular relationship exists between childhood asthma and OSA.
- Hub genes LRP3, BAK1, and CLIC4 are critical in the interplay between these conditions.
- The findings highlight potential therapeutic targets for managing comorbid asthma and OSA in children.
Abstract:
Childhood asthma is a common chronic respiratory disorder influenced by various factors, and obstructive sleep apnea (OSA) has emerged as a significant comorbidity. This study sought to investigate the underlying molecular mechanisms of the comorbidity between childhood asthma and OSA through Mendelian randomization (MR) analysis. Gene expression and genotype data were analyzed from public databases, and single nucleotide polymorphisms (SNPs) related to both diseases were identified. Our research findings unveiled 242 gene pairs associated with childhood asthma and 350 gene pairs related to OSA. Among them, the three hub genes, namely LRP3, BAK1, and CLIC4, exhibited significant expression alterations in both diseases. These hub genes participate in multiple signal transduction pathways and exhibit a remarkable correlation with the infiltration of immune cells, suggesting that they exert a vital role in modulating the immune microenvironment. Further analyses, encompassing gene set enrichment and transcriptional regulation, emphasized the complex interplay between these genes and non-coding RNAs as well as transcription factors. Our study results stressed the bidirectional relationship between childhood asthma and OSA and accentuated the significance of early identification and targeted intervention. This study identified potential therapeutic targets and laid a foundation for formulating treatment strategies aimed at improving the conditions of children with these interrelated diseases.
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