Potential Causal Relationship Between Extensive Lipid Profiles and Various Hair Loss Diseases: Evidence From Univariable and Multivariable Mendelian Randomization Analyses

Background: Hair loss disorders, including non-cicatricial forms such as alopecia areata (AA) and androgenetic alopecia (AGA), as well as cicatricial forms, represent significant dermatological concerns influenced by various factors, including lipid metabolism. While observational studies and clinical trials have suggested a link between lipid levels and hair loss, the causal relationship remains unclear. Methods: We conducted a comprehensive analysis of 983 lipid variables [including triglycerides (TG), fatty acids, cholesterol, cholesterol esters, phospholipids, and lipoproteins] and 4 hair loss disorders. Two-sample univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) analyses were employed to investigate the causal effects of lipids on hair loss disorders. Sensitivity analyses were performed to ensure the robustness of our findings. Results: The UVMR analysis identified 56 significant causal associations between lipid levels and hair loss disorders, with cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), TG, apolipoprotein A1, apolipoprotein B, and lipoprotein(a) emerging as key contributors. The MVMR analysis evaluated the independent effects of HDL-C, LDL-C, and TG on alopecia disorders, identifying significant associations only between HDL-C, TG, and AA. Sensitivity analyses confirmed the consistency and robustness of these results. Conclusion: This study provides strong evidence for potential causal associations between lipids and hair loss disorders, highlighting potential therapeutic targets and the importance of lipid management in affected patients.