Causal relationship between schizophrenia and five types of dementia: A bidirectional two-sample Mendelian...

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Observational studies suggest an association between schizophrenia and dementia.
• The causal relationship between schizophrenia and various dementia types remains unclear.

Purpose of the Study:

• To investigate the causal relationship between schizophrenia and five dementia types: all-cause dementia, Alzheimer's disease, vascular dementia, frontotemporal dementia, and dementia with Lewy bodies.
• To conduct a bidirectional two-sample Mendelian randomization analysis.

Main Methods:

• Utilized pooled genome-wide association study (GWAS) statistics from European ancestry individuals.
• Employed inverse variance weighted (IVW) as the primary Mendelian randomization method.
• Conducted sensitivity analyses including MR-Egger, weighted median, cML-MA, and pleiotropy/heterogeneity assessments.

Main Results:

• Schizophrenia was associated with an increased risk of all-cause dementia (OR=1.065, P=0.001), Alzheimer's disease (OR=1.029, P=0.027), and vascular dementia (OR=1.106, P=0.012).
• No significant causal effect of any dementia type on schizophrenia risk was observed.

Conclusions:

• Schizophrenia may be a causal risk factor for all-cause dementia, Alzheimer's disease, and vascular dementia.
• Dementia was not identified as a risk factor for schizophrenia in this study.
• The findings provide insights into the potential genetic relationship between schizophrenia and dementia.