Functional enrichment analysis of mutated genes in children with hyperthyroidism

ObjectiveHyperthyroidism 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.MethodsWhole-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.ResultsThrough 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.ConclusionThe 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.

Automated summary

This study aims to explore the functions and gene sets of mutated genes related to hyperthyroidism in children. Through gene ontology and biological signaling pathway analysis, it was found that hormone activity and response to peptide hormone are the most significant gene ontology functions and thyroid hormone signaling pathway is the most significant biological signaling pathway. The identified mutated genes provide insights into the expected effects of multiple mutated genes on hyperthyroidism in children.