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The relationship between major depression and delirium: A two-sample Mendelian randomization analysis
Jing Li1, Jiachen Wang2, Mingyi Yang2
1Department of Anesthesiology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China.
Background:
Major depression (MD) is a well-recognized risk factor for delirium. However, observational studies cannot provide direct evidence of causality between MD and delirium.
Methods:
This study explored the genetic causal association between MD and delirium using two-sample Mendelian randomization (MR). Genome-wide association study (GWAS) summary data for MD were obtained from the UK Biobank. GWAS summary data for delirium were obtained from the FinnGen Consortium. Inverse-variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode were used to perform the MR analysis. In addition, the Cochrane's Q test was used to detect heterogeneity in the MR results. Horizontal pleiotropy was detected using the MR-Egger intercept test and MR pleiotropy residual sum and outliers (MR-PRESSO) test. Leave-one-out analysis was used to investigate the sensitivity of this association.
Results:
The IVW method showed that MD was an independent risk factor for delirium (P = 0.013). Horizontal pleiotropy was unlikely to bias causality (P > 0.05), and no evidence of heterogeneity was found between the genetic variants (P > 0.05). Finally, a leave-one-out test showed that this association was stable and robust.
Limitations:
All participants included in the GWAS were of European ancestry. Due to database limitations, the MR analysis did not conduct stratified analyses for different countries, ethnicities, or age groups.
Conclusion:
We conducted a two-sample MR analysis and found the evidence of genetic causal association between MD and delirium.
Insights
Major depression (MD) is a risk factor for delirium. Mendelian randomization analysis found genetic evidence supporting a causal link between MD and an increased risk of delirium.
Area of Science:
- Psychiatry
- Genetics
- Epidemiology
Background:
- Major depression (MD) is a recognized risk factor for delirium.
- Observational studies are limited in establishing a direct causal relationship between MD and delirium.
Purpose of the Study:
- To investigate the potential genetic causal association between major depression and delirium.
- Utilize two-sample Mendelian randomization (MR) to assess causality.
Main Methods:
- Employed two-sample Mendelian randomization (MR) analysis.
- Utilized genome-wide association study (GWAS) summary data for MD (UK Biobank) and delirium (FinnGen Consortium).
- Applied various MR methods including Inverse-variance weighted (IVW), MR Egger, and weighted median, alongside heterogeneity and pleiotropy tests.
Main Results:
- The IVW method indicated that MD is an independent risk factor for delirium (P = 0.013).
- No significant evidence of heterogeneity or horizontal pleiotropy was found, suggesting robust causality.
- Leave-one-out analysis confirmed the stability and reliability of the association.
Conclusions:
- This study provides genetic evidence for a causal association between major depression and delirium.
- The findings support MD as a significant risk factor contributing to the development of delirium.
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