The causal effects of dementia on systemic sclerosis: a two-sample bidirectional Mendelian randomization study

Area of Science:

• Neuroscience
• Rheumatology
• Genetics

Background:

• Systemic sclerosis (SSc) is increasingly linked to cognitive impairment and dementia.
• The precise causal relationship and its directionality between SSc and dementia remain unclear.
• This study investigates the genetic links between five dementia types and SSc.

Purpose of the Study:

• To evaluate the potential genetic causal relationship between five types of dementia and systemic sclerosis (SSc).
• To determine the directionality of any observed causal links using bidirectional Mendelian randomization.

Main Methods:

• Employed a two-sample bidirectional Mendelian randomization (MR) approach using genome-wide association study (GWAS) data.
• Utilized the inverse variance weighted (IVW) method as primary analysis, with weighted median, MR-Egger, and mode methods for validation.
• Conducted sensitivity analyses, pleiotropy tests, and heterogeneity assessments to ensure result reliability.

Main Results:

• A significant inverse causal association was found between Alzheimer's disease (AD) and the risk of SSc (IVW OR = 0.530, P = 0.039).
• No significant causal relationships were identified between SSc and frontotemporal dementia, vascular dementia, dementia with Lewy bodies, or Parkinson's disease dementia.
• Reverse MR analysis confirmed no causal effect of SSc on dementia risk, and sensitivity analyses indicated robust findings.

Conclusions:

• The study provides evidence for a potential causal link between AD and a reduced risk of developing SSc.
• These findings underscore the need for further investigation into the biological mechanisms underlying the relationship between AD and SSc.