A Bidirectional Mendelian Randomization Study of Androgenetic Alopecia and Obesity.

Background: Androgenetic alopecia (AGA) is a prevalent hereditary hair follicle disorder. Multiple observational epidemiological researches have reported an observational correlation between obesity and AGA onset, whereas reliable evidence supporting their intrinsic causal association is lacking. Methods: Bidirectional two-sample Mendelian randomization (MR) design was performed to explore causal links between obesity and AGA. The inverse variance weighted (IVW) random-effects model was set as the primary causal estimation method, supplemented with weighted median, MR-Egger, simple mode and weighted mode approaches. Multiple sensitivity analyses, including heterogeneity evaluation, horizontal pleiotropy detection and leave-one-out analysis, were conducted to verify result robustness. Results: Forward MR (obesity→AGA) identified no statistically significant causal effect of obesity on AGA risk (IVW OR=1.01, 95% CI 0.98-1.04, P=0.58). Consistently, reverse MR (AGA→obesity) failed to verify a causal influence of AGA on obesity (IVW OR=1.00, 95% CI 0.99-1.01, P=0.83). Subsequent pleiotropy testing and leave-one-out sensitivity analyses yielded concordant outcomes without detectable horizontal pleiotropic bias. Conclusion: This MR analysis excludes bidirectional causal associations between obesity and AGA. Previously observed epidemiological correlations between the two phenotypes are plausibly driven by confounding variables rather than direct causation, providing novel genetic epidemiological evidence for AGA pathogenic exploration.