Genetic Association between Obesity, Arm Fat Percentage, Leg Fat Percentage, and Risk of Migraine: A Two-Sample Mendelian Randomization Study

Abstract

Abstract Background: Migraine, a prevalent neurological disorder, has attracted considerable attention due to its complex etiology and potential links with traits related to obesity. This study utilizes a robust two-sample Mendelian randomization (MR) framework to explore potential genetic connections between obesity, arm fat percentage (AFP, left), leg fat percentage (LFP, right), and migraine risk. Methods: This study conducted a rigorous two-sample Mendelian randomization (MR) analysis using comprehensive summary-level data from genome-wide association studies (GWAS) involving obesity, AFP (left), LFP (right), and migraine. Genetic instruments were carefully chosen based on firmly established connections with the corresponding traits. The MR analysis employed various methods, including inverse variance weighted (IVW), weighted median, and MR-Egger, to evaluate causal relationships and potential pleiotropy. Results: The findings offer strong evidence indicating a possible causal link between obesity and a decreased migraine risk (IVW: odds ratio [OR] = 0.91, 95% confidence interval [CI] = 0.85–0.97). Moreover, the MR analysis indicates a comparable potential causal connection between arm fat percentage (left) and a reduced risk of migraine (IVW: OR = 0.85, 95% CI = 0.75–0.98). However, no substantial causal link was found between leg fat percentage (right) and migraine risk in this study (IVW: OR = 0.99, 95% CI = 0.85–1.16). Conclusion: This two-sample Mendelian randomization investigation illuminates the complex interplay between obesity-related traits and migraine risk. The findings imply a potential protective effect of obesity and arm fat percentage (left) against migraine risk, suggesting a novel approach for investigating preventive strategies. In contrast, there was no substantial causal connection observed between leg fat percentage (right) and migraine risk. These findings emphasize the significance of additional research to clarify the underlying mechanisms and clinical implications of these associations.