Causal associations between sleep traits and age at natural menopause: A Mendelian randomization study

Observational studies have revealed that several sleep traits can impact ovarian function in women. However, there is no evidence suggesting associations between sleep traits and age at natural menopause (ANM). The objective of this study was to investigate the causal relationship between sleep traits (insomnia, sleep duration, daytime sleepiness) and ANM from the perspective of genetic variation. We selected the single-nucleotide polymorphisms from large-scale genome-wide association studies as instrumental variables and conducted a two-sample Mendelian randomization (MR) analysis on these single-nucleotide polymorphisms, including inverse variance weighting, MR-Egger, weighted median, simple mode and weighted mode. The Steiger test was employed to verify the correct causal directionality. The robustness of the MR analysis was examined through Cochran's Q test, horizontal pleiotropy test, and leave-one-out analysis. The results indicated that insomnia was causally associated with ANM (inverse variance weighting: β = -0.982; 95% CI: -1.852 to -0.111, P = .027), with other analyses confirming the robustness of this finding. Steiger test and reverse MR Analysis validated the absence of a reverse causal association between the two. However, sleep duration and daytime sleepiness did not exhibit a causal effect on ANM. In summary, this study provides initial evidence that insomnia can contribute to an earlier onset of ANM. Nevertheless, further clinical studies are needed to elucidate these findings.