Exploratory study of cold hypersensitivity in Japanese women: genetic associations and somatic symptom burden

Abstract

Temperature perception is essential for humans to discern the environment and maintain homeostasis. However, some individuals experience cold hypersensitivity, characterized by a subjective feeling of coldness despite ambient environmental temperatures being normal, the underlying mechanisms of which are unknown. In this study, we aimed to investigate the relationship between subjective cold symptoms and somatic burden or single nucleotide polymorphisms to understand the causes of cold hypersensitivity. We conducted an online questionnaire survey [comprising 30 questions, including past medical history, subjective symptoms of cold hypersensitivity, and the Somatic Symptom Scale-8 (SSS-8)]. Respondents were 1200 Japanese adult female volunteers (age: 20–59 years), recruited between April 21 and May 25, 2022, who were customers of MYCODE, a personal genome service in Japan. Among the 1111 participants, 599 (54%) reported cold hypersensitivity. Higher cold hypersensitivity severity was positively associated with the SSS-8 scores. Additionally, a genome-wide association study for cold hypersensitivity was conducted using array-based genomic data obtained from genetic testing. We identified 11 lead variants showing suggestive associations (P < 1 × 10–5) with cold hypersensitivity, some of which showed a reasonable change in expression in specific tissues in the Genotype-Tissue Expression database. The study findings shed light on the underlying causes of cold hypersensitivity.

A new biomarker for screening of Hiesho (cold sensation) in young females through feet temperature recovery rate after cooling test

“…Recent research further supports this notion, indicating that Hiesho is not a uniform health issue and may have genetic underpinnings. Wu et al identified decreased expression of genes TRPM2 and KCNK2 in Hiesho patients, which are associated with temperature regulation and sensation [19]. This diminished gene activity likely leads to heightened sensitivity to cold temperatures and impairs heat dissipation, potentially explaining the observed lower temperature recovery rates in individuals with Hiesho.…”