ArticleGenetics research2025
Exploring Genetic Markers for Cold-Heat Patterns: Integrating Traditional Medicine With Modern Genomic Research.
Article in Genetics research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Temperature sensitivity has gained considerable attention in the era of precision medicine. This trait has long been used to identify cold-heat patterns (C-HPs), a diagnostic framework in Traditional Korean Medicine that categorizes individuals based on their thermal responses. C-HP helps understand an individual's inherent physical characteristics, which have been shown to be highly heritable and thus shaped by genetic factors. However, genetic markers that are significantly associated with this trait remain scarce. To address this gap, we aimed to identify candidate single-nucleotide polymorphisms (SNPs) based on previous genomewide association studies (GWASs) of related traits. Methods: Given the limited research directly addressing C-HP, we incorporated genetic studies related to traits such as "Cold" or "Heat," as well as thyroid hormone, which plays a key role in thermogenesis through the activation of various metabolic pathways. After selecting the SNPs reported in previous GWAS from the GWAS Catalog (EMBL-EBI), we validated these findings using 90 Korean patients reporting C-HP, with statistical significance assessed through residual permutations. Gene set enrichment analysis (GSEA) was performed using the GO Biological Process 2023 dataset to identify the pathways associated with C-HP. Furthermore, we compared our findings with control traits in order to confirm that the observed associations were specific to C-HP-related traits rather than random correlations. Principal component analysis (PCA) was conducted on candidate SNPs from the 1000 Genomes reference dataset to illustrate the ethnic variation for C-HP across five populations. Results: Of 63 GWAS, we selected 548 SNPs for validation. Ultimately, 20 candidate SNPs associated with heat patterns and 19 candidate SNPs associated with cold patterns were identified. Of the heat-pattern SNPs, 18 were linked to thyroid hormone traits, with key SNPs including rs12409301 ( Conclusion: Our study suggested a total of 39 candidate SNPs as genetic markers for C-HP that are plausible in the context of temperature sensitivity. We hope that our findings will provide a valuable basis for further biological research and potential clinical applications of C-HP.
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