Causal Association Between Allergic Diseases and Dementia: Evidence from Multivariate Mendelian Randomization Study

Area of Science:

• Neuroscience
• Genetics
• Immunology

Background:

• The relationship between allergic diseases and dementia is debated, with unclear genetic links.
• Previous observational studies suggest associations, but causality remains unproven.

Purpose of the Study:

• To investigate the causal relationship between allergic diseases and dementia using Mendelian randomization (MR).
• To differentiate true causal effects from confounding factors in the allergy-dementia association.

Main Methods:

• Utilized univariate and multivariate Mendelian randomization (MR) on genome-wide association study data from the FinnGen Consortium.
• Included 66,645 allergic disease cases and 12,281 dementia cases of European ancestry.
• Employed inverse variance weighting and MR-Egger methods, with sensitivity analyses including Cochran's Q test and MR-PRESSO.

Main Results:

• Atopic dermatitis showed a causal link to reduced vascular dementia (VaD) risk.
• Asthma was associated with reduced risk for Alzheimer's disease (AD) and potentially VaD.
• Allergic rhinitis demonstrated a potential causal association with increased risk for both AD and VaD.

Conclusions:

• Mendelian randomization suggests allergic rhinitis is causally linked to increased dementia risk.
• Other allergic diseases' associations with dementia may be due to confounding factors, not direct causality.
• Findings highlight specific allergic conditions' potential differential impact on dementia subtypes.