Genetic Insights Into Dietary Factors, Metabolic Traits and Myasthenia Gravis Risk: A Large-Scale Two-Sample Mendelian Randomization Study in European Populations

Abstract

The impact of dietary factors and metabolic traits on the risk of myasthenia gravis (MG) is not well understood. This study utilized two-sample Mendelian randomization (MR) to investigate the causal relationships between 16 dietary factors and 10 metabolic traits with MG risk. Using the inverse variance weighted (IVW) method, we identified significant causal associations and tested for heterogeneity using Cochran's Q test. The MR-Egger intercept was used to assess horizontal pleiotropy, and the Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) framework was applied to detect and correct for potential outliers. Our analysis revealed that increased fresh fruit intake was associated with a reduced risk of MG (odds ratio [OR] = 0.023, 95% confidence interval [CI] = 0.001–0.683, p = 0.029). In contrast, higher body mass index (BMI) (OR = 2.696; 95% CI = 1.524–4.770; p < 0.001), waist circumference (OR = 2.995, 95% CI = 1.457–6.156, p = 0.003), hypothyroidism (OR = 1.337, 95% CI = 1.033–1.730, p = 0.027), and hyperthyroidism (OR = 2.240, 95% CI = 1.001–4.683, p < 0.001) were positively associated with MG risk. After adjusting for the false discovery rate (FDR), BMI and hyperthyroidism remained significantly linked to MG. No significant associations were found between MG and the other 15 dietary factors or 6 metabolic traits. These findings highlight the potential nutritional and metabolic pathways that may contribute to MG risk, suggesting that dietary interventions, particularly increasing fruit intake, and managing metabolic factors like BMI and thyroid health could play a role in the prevention and management of MG.