A suggested shared aetiology of dementia - a colocalization study

Area of Science:

• Genetics
• Neurology
• Epidemiology

Background:

• Dementia and its clinical outcomes often occur together, indicating shared underlying causes.
• Identifying shared genetic factors can elucidate the aetiology and multimorbidity of dementia.

Purpose of the Study:

• To detect shared causal genes between dementia or Alzheimer's disease (AD) and related traits using genetic data.
• To explore potential biological pathways involved in shared aetiology.

Main Methods:

• Utilized HyPrColoc analysis on UK Biobank GWAS summary results for dementia/AD and five traits: stroke, diabetes, atherosclerosis, cholesterol, and alcohol consumption.
• Focused on 601 dementia/AD-associated genetic regions.
• Performed functional analysis on candidate causal genes.

Main Results:

• Identified a shared causal variant (rs150562240 in LPIN3) for dementia, AD, and atherosclerosis.
• Found evidence of colocalization between dementia and stroke (2 regions), dementia/AD and atherosclerosis (6 regions), and dementia/AD and diabetes (2 regions).
• Detected colocalization signals between diabetes and other non-dementia/AD traits in 5 regions.

Conclusions:

• The study provides genetic evidence supporting a shared aetiology between dementia and related diseases, including stroke, atherosclerosis, and diabetes.
• Findings highlight potential shared genetic pathways contributing to multimorbidity in dementia patients.