The relationship between major depressive disorder and dementia: A bidirectional two-sample Mendelian randomization
Yijun Hu1, Yuntao Zou2, Meng Zhang1
1Institute of Acupuncture and Moxibustion, Shandong University of Traditional Chinese Medicine, Jinan, China; Innovation Research Institute of Chinese Medicine, Shandong University of Traditional Chinese Medicine, China.
Background:
Major depressive disorder (MDD) and dementia psychiatric and neurological diseases that are clinically widespread, but whether there is a causal link between them is still unclear. In this study, bidirectional two-sample Mendelian randomization (MR) was used to investigate the potential causal relationship between MDD and dementia via a genome-wide association study (GWAS) database, containing samples from the European population.
Method:
We collected data on MDD and common clinical dementia subtypes from GWAS, including Alzheimer's disease (AD), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD), and vascular dementia (VaD). A series of bidirectional two-sample MR studies and correlation sensitivity analysis were carried out.
Results:
In the study of the effect of MDD on dementia subtypes, no causal relationship was found between MDD and dementia subtypes other than VaD, inverse variance weighted (IVW) method: odds ratio (OR), 2.131; 95 % confidence interval (CI), 1.249-3.639, P = 0.006; MDD-AD: OR, 1.000; 95 % CI, 0.999-1.001, P = 0.537; MDD-FTD: OR, 1.476; 95 % CI, 0.471-4.627, P = 0.505; MDD-PDD: OR, 0.592; 95 % CI, 0.204-1.718, P = 0.335; MR-Egger method: MDD-DLB: OR, 0.582; 95 % CI, 0.021-15.962, P = 0.751. In reverse MR analyses, no dementia subtype was found to be a risk factor for MDD.
Limitations:
The results of this study may not be generalizable to non-European populations.
Conclusion:
MDD was identified as a potential risk factor for VaD, but no dementia subtype was found to be a risk factor for MDD. These results suggest a new avenue for the prevention of VaD.
Insights
Major depressive disorder (MDD) is a risk factor for vascular dementia (VaD). However, dementia subtypes do not increase the risk for MDD. These findings offer new insights into VaD prevention strategies.
Area of Science:
- Neuroscience
- Psychiatry
- Genetics
Background:
- Major depressive disorder (MDD) and dementia are prevalent neurological and psychiatric conditions.
- The causal relationship between MDD and dementia remains unclear.
- Investigating this link is crucial for understanding disease mechanisms and prevention.
Purpose of the Study:
- To investigate the potential bidirectional causal relationship between MDD and various dementia subtypes.
- To utilize genome-wide association study (GWAS) data for robust genetic analysis.
- To explore genetic links in European populations.
Main Methods:
- Bidirectional two-sample Mendelian randomization (MR) analysis.
- Utilized GWAS summary statistics for MDD and dementia subtypes (AD, FTD, DLB, PDD, VaD).
- Performed correlation sensitivity analyses to ensure result validity.
Main Results:
- MDD was identified as a potential risk factor for vascular dementia (VaD) (OR, 2.131; P=0.006).
- No significant causal link was found between MDD and Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies, or Parkinson's disease with dementia.
- Reverse MR analyses showed no dementia subtype as a risk factor for MDD.
Conclusions:
- MDD may be a significant risk factor for developing VaD.
- No evidence suggests dementia subtypes increase the risk of MDD.
- Findings highlight a potential pathway for VaD prevention.
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