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Functional enrichment analysis of mutated genes in children with hyperthyroidism
Xiaojian Mao1, Liangliang Tang2, Hongyi Li1
1Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, China.
Insights
This study identifies key mutated genes in Chinese children with hyperthyroidism, linking them to hormone activity and thyroid hormone signaling pathways for better understanding and potential treatment strategies.
Area of Science:
- Genetics and Molecular Biology
- Pediatric Endocrinology
- Genomics
Background:
- Hyperthyroidism in Chinese children is a growing concern with significant health implications.
- As a polygenic disorder, hyperthyroidism presents complex challenges in prediction and treatment compared to monogenic diseases.
Purpose of the Study:
- To elucidate the functions and gene sets associated with mutated genes in pediatric hyperthyroidism.
- To enhance understanding of the impact of multiple mutated genes on hyperthyroidism in children through gene ontology and pathway analysis.
Main Methods:
- Whole-exome sequencing was conducted on DNA samples from children diagnosed with hyperthyroidism.
- Pathogenic genes were identified using public databases (Malacards, MutationView, Clinvar) and analyzed via statistical and gene enrichment approaches.
Main Results:
- Gene Ontology (GO) enrichment analysis revealed significant associations with "hormone activity" and "response to peptide hormone".
- Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis highlighted the "Thyroid hormone signaling pathway" and "Hypertrophic cardiomyopathy" pathways.
- Specific gene sets including TG, CALCA, POMC, TSHR, and others were identified as commonly affecting hyperthyroidism in children.
Conclusions:
- Mutated genes in pediatric hyperthyroidism are strongly associated with "hormone activity" and "response to peptide hormone" functions.
- The study identified critical biological signaling pathways, including the "Thyroid hormone signaling pathway" and "Hypertrophic cardiomyopathy", implicated in the disease.
- Findings provide insights into the genetic underpinnings of hyperthyroidism in children, potentially guiding future diagnostic and therapeutic interventions.
Objective:
Hyperthyroidism in Chinese children is relatively high and has been increasing in recent years, which has a significant impact on their healthy development. Hyperthyroidism is a polygenic disorder that presents greater challenges in terms of prediction and treatment than monogenic diseases. This study aims to elucidate the associated functions and gene sets of mutated genes in children with hyperthyroidism in terms of the gene ontology through GO enrichment analysis and in terms of biological signaling pathways through KEGG enrichment analysis, thereby enhancing our understanding of the expected effects of multiple mutated genes on hyperthyroidism in children.
Methods:
Whole-exome sequencing was performed on the DNA samples of children with hyperthyroidism. Screening for pathogenic genes related to hyperthyroidism in affected children was performed using the publicly available disease databases Malacards, MutationView, and Clinvar, and the functions and influences of the identified pathogenic genes were analyzed using statistical analysis and the gene enrichment approach.
Results:
Through GO enrichment analysis, it was found that the most significant gene ontology enrichment was the function "hormone activity" in terms of gene ontology molecular function. The corresponding mutated genes set that has common effects on hyperthyroidism in children included TG, CALCA, POMC, CGA, PTH, GHRL, FBN1, TRH, PRL, LEP, ADIPOQ, INS, GH1. The second most significant gene ontology enrichment was the function "response to peptide hormone" in terms of biological process. The corresponding mutated genes set that has common effects on hyperthyroidism in children included LRP6, TSC2, KANK1, COL1A1, CDKN1B, POMC, STAT1, MEN1, APC, GHRL, TSHR, GJB2, FBN1, GPT, LEP, ADIPOQ, INS, GH1. Through KEGG enrichment analysis, it was found that the most significant biological signaling pathway enrichment was the pathway "Thyroid hormone signaling pathway" function. The corresponding mutated genes set that has common effects on hyperthyroidism in children included NOTCH3, MYH7, TSC2, STAT1, MED13L, MAP2K2, SLCO1C1, SLC16A2, and THRB. The second most significant biological signaling pathway enrichment was the pathway "Hypertrophic cardiomyopathy" in terms of biological process. The corresponding mutated genes set that has common effects on hyperthyroidism in children included IGF1, CACNA1S, MYH7, IL6, TTN, CACNB2, LAMA2, and DMD.
Conclusion:
The mutated genes in children with hyperthyroidism were closely linked to function involved in "hormone activity" and "response to peptide hormone" in terms of the biological signaling pathway, and to the functional pathways involved in "Thyroid hormone signaling pathway" and "Hypertrophic cardiomyopathy" in terms of the biological signaling pathway.
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