Association Between Androgenetic Alopecia and Schizophrenia: A Bidirectional Mendelian Randomization Study

Objective: Hair diseases are associated with mental illness. However, the relationship between schizophrenia and androgenetic alopecia (AGA) is lacking. In this study, we explored the causal relationship between AGA and schizophrenia using Mendelian randomization (MR) analysis. Methods: A bidirectional MR analysis was conducted to determine the causal relationship between AGA and schizophrenia using data from the IEU OpenGWAS database (https://gwas.mrcieu.ac.uk/). The methods used for forward and reverse MR analyses included the inverse variance weighted method, MR-Egger method, weighted median, weighted mode, and simple mode approaches. Heterogeneity was assessed with the MR-Egger and inverse variance weighted methods, and Cochran’s Q test was used to evaluate heterogeneity. MR-Egger regression was used to assess pleiotropy, and a leave-one-out method was applied to evaluate the dependence of MR results on specific single-nucleotide polymorphisms (SNPs). Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed for genes influencing the causal relationship between exposure and outcome at SNP sites. Results: Forward MR analysis revealed a significant causal relationship between AGA and schizophrenia (odds ratio [95% confidence interval], 0.996 [0.992–0.999]; P = 0.025), while reverse MR analysis showed no causal association between schizophrenia and AGA (odds ratio [95% confidence interval], 1.061 [0.965–1.165]; P = 0.220). No heterogeneity or pleiotropy was observed. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genome pathway analyses indicated that affected genes at SNP sites in forward MR analysis were associated with pyrimidine metabolism, nucleotide metabolism, galactose metabolism, ion activity, the mammalian target of rapamycin signaling pathway, and RNA degradation. Conclusion: A causal relationship between AGA and schizophrenia was identified in forward MR analysis, while schizophrenia showed no causal association with AGA in reverse MR analysis.