Insomnia and Alopecia Areata: A Causal Relationship Revealed by Mendelian Randomization

Moon status disturbance, such as psychological stress, anxiety, and depression, have been discussed as key factors that may trigger alopecia areata (AA). However, the relationship between insomnia and AA has not been thoroughly explored. In a study by Seo et al., it was found that insomnia patients had a higher incidence of acquiring AA (log-rank p < 0.001) [8]. A population-based cohort study conducted in Taiwan, which recruited 5648 AA patients and 22,592 controls, reported a potential bidirectional cause-effect association between AA and insomnia [33]. However, another study using a questionnaire found no association between sleeping habits and androgenetic alopecia (AGA) [27]. This finding is consistent with our Mendelian randomization (MR) analysis, which suggests that insomnia has a causal relationship with AA, but not with AGA. This causal relationship may be related to the pathological mechanism of AA. As an autoimmune disease, lymphocytic infiltrations around the hair follicle and IFN-γ mediated inflammation lead to the decay of hair follicle immune privilege and disruption of the hair cycle, making it the dominant pathological mechanism of AA [34]. Insomnia is known to induce a downregulation of adaptive immunity, along with an upregulation of innate immune responses, which can ultimately exacerbate autoimmune diseases [35]. Therefore, it is important to prioritize sleep quality in the clinical management of AA.

Drawing significant causal conclusions on the potentially harmful association between body mass index (BMI) and AGA observed in this MR study is not yet possible. A cross-sectional study involving 351 Caucasian subjects with AGA found that BMI and smoking were associated with an increased risk of AGA [36]. Another observational study of young Finnish men (n=737) with AGA found that AGA patients had a higher BMI and larger waist circumference than the control group [37]. A questionnaire study found that a high BMI was significantly related to AA (OR, 1.15; P = 0.021) [38]. During obesity, a large number of adipocytes produce inflammatory cytokines, which can reach peripheral areas such as hair follicles. The release of inflammatory factors, such as interferon (IFN)-γ, can promote the expression of MHC class I/II in hair follicles and trigger AA [38]. However, our MR study was unable to establish a causal relationship between waist circumference and non-scarring alopecia. It is important to note that research results should not solely depend on a P-value threshold, and considering various outcomes should be advantageous in the study. Therefore, we propose that the impact of BMI on AGA should be valued rather than dismissing potentially important data [39].

A cross-sectional study revealed that AGA is significantly associated with a sedentary lifestyle [6]. Another large-sample cross-sectional analysis, which included 3555 older adults in England, found no association between low socioeconomic background (LSB) and hair cortisol [40]. Our MR analysis agrees with the opinion that LSB is not causally related to alopecia.