Background: Numerous observational studies have documented an association between the circadian rhythm and the composition of the gut microbiota. However, the bidirectional causal effect of the morning chronotype on the gut microbiota is unknown. Methods: A two-sample Mendelian randomization study was performed, using the summary statistics of the morning chronotype from the European Consortium and those of the gut microbiota from the largest available genome-wide association study meta-analysis, conducted by the MiBioGen consortium. The inverse variance-weighted (IVW), weighted mode, weighted median, MR-Egger regression, and simple mode methods were used to examine the causal association between the morning chronotype and the gut microbiota. A reverse Mendelian randomization analysis was conducted on the gut microbiota, which was identified as causally linked to the morning chronotype in the initial Mendelian randomization analysis. Cochran’s Q statistics were employed to assess the heterogeneity of the instrumental variables. Results: Inverse variance-weighted estimates suggested that the morning chronotype had a protective effect on Family Bacteroidaceae (β = −0.072; 95% CI: −0.143, −0.001; p = 0.047), Genus Parabacteroides (β = −0.112; 95% CI: −0.184, −0.039; p = 0.002), and Genus Bacteroides (β = −0.072; 95% CI: −0.143, −0.001; p = 0.047). In addition, the gut microbiota (Family Bacteroidaceae (OR = 0.925; 95% CI: 0.857, 0.999; p = 0.047), Genus Parabacteroides (OR = 0.915; 95% CI: 0.858, 0.975; p = 0.007), and Genus Bacteroides (OR = 0.925; 95% CI: 0.857, 0.999; p = 0.047)) demonstrated positive effects on the morning chronotype. No significant heterogeneity in the instrumental variables, or in horizontal pleiotropy, was found. Conclusion: This two-sample Mendelian randomization study found that Family Bacteroidaceae, Genus Parabacteroides, and Genus Bacteroides were causally associated with the morning chronotype. Further randomized controlled trials are needed to clarify the effects of the gut microbiota on the morning chronotype, as well as their specific protective mechanisms.

Background: The causal connection between morning diurnal preference and psychiatric disorders remains enigmatic. Using bidirectional two-sample Mendelian randomization (MR), we aim to explore the potential causal associations between morning diurnal preference and seven prominent psychiatric disorders. Methods: MR is a genetic epidemiological method that leverages genetic variants as instrumental variables to infer causal associations between exposures and outcomes. We obtained morning diurnal preference data from genome-wide association study (GWAS) datasets and identified 252,287 individuals as morning people. Psychiatric disorder data were sourced from the FinnGen consortium R9 dataset. Our primary analysis used the inverse-variance weighted (IVW) approach to evaluate the overall causal effect by combining the estimates from each genetic variant. Addition analyses, including weighted median, MR-Egger regression, weighted mode, and simple mode techniques were conducted to ensure robustness. Results: Being a morning person is related to reduced odds of multiple psychiatric disorders, including depression or dysthymia (OR: 0.93, 95% CI: 0.88, 0.999), anxiety disorders (OR: 0.90, 95% CI: 0.84, 0.96), self-harming behaviors (OR: 0.87, 95% CI: 0.76, 0.99), substance-use disorders (OR: 0.81, 95% CI: 0.71, 0.93), alcohol dependence (OR: 0.82, 95% CI: 0.73, 0.92), alcohol use disorders (OR: 0.85, 95% CI: 0.76, 0.94), acute alcohol intoxication (OR: 0.86, 95% CI: 0.76, 0.96), schizophrenia (OR: 0.77, 95% CI: 0.65, 0.92), and schizophrenia or delusion (OR: 0.80, 95% CI: 0.70, 0.92). Alcohol dependence (OR: 0.97, 95% CI: 0.94, 0.999) and alcohol use disorders (OR: 0.96, 95% CI: 0.94, 0.99) were also related to a lower morning diurnal preference. Conclusions: Our study provides evidence that being a morning person is a protective factor for various psychiatric disorders from a genetic perspective. The results provide insights for potential targeted interventions to improve mental wellbeing.