Objective: While numerous studies have highlighted an increased prevalence of depression in individuals with narcolepsy, their conclusions are often clouded by potential confounding factors, leaving the causal relationship uncertain. This study posits that narcolepsy might heighten the risk of depression and employs a two-sample Mendelian randomization analysis to investigate this hypothesis.
Methods: Summary statistics were obtained from genome-wide association studies databases and performed a two-sample MR analysis. The inverse-variance weighted method was employed as the primary approach to evaluate causality. Additionally, supplementary methods were conducted, including MR-Egger, simple median, maximum likelihood, weighted median, penalized weighted median, and weighted mode, to complement the IVW results. Finally, sensitivity analyses were undertaken to assess heterogeneity, horizontal pleiotropy, and stability of the results.
Results: The inverse-variance weighted analysis revealed an odds ratio of 1.055 with a 95% confidence interval of 1.015 to 1.097, indicating a significant positive association between narcolepsy and depression. Although significant heterogeneity was observed (Q = 56.22, p = 0.0005), no evidence of horizontal pleiotropy was detected (intercept = -0.00027, p = 0.69). Results from the additional methods were in agreement with those obtained from the inverse-variance weighted analysis. The reverse causality of depression on narcolepsy was not detected (p = 0.11).
Conclusion: This study suggests a potential causal association between narcolepsy and depression. While the findings offer insights into this relationship, they should be interpreted with caution, especially considering the limitations of the data. Further research is needed to better understand the underlying mechanisms and to explore potential interventions.
Keywords: Causal relationship; Depression; Mendelian randomization; Narcolepsy; Single-nucleotide polymorphisms.
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