A suggested shared aetiology of dementia - a colocalization study

Abstract

Identification of shared causal genes between dementia and its related clinical outcomes can help understand shared aetiology and multimorbidity surrounding dementia. We performed the HyPrColoc colocalization analysis to detect possible shared causal genes between dementia or Alzheimer's disease (AD) and 5 selected traits: stroke, diabetes, atherosclerosis, cholesterol level, and alcohol consumption within 601 dementia or AD associated genetic regions using summary results of the UK Biobank genome-wide association studies. Functional analysis was performed on the candidate causal genes to explore potential biological pathways. Rs150562240 in the LPIN3 gene was identified as a candidate shared causal variant across dementia, AD and atherosclerosis. Evidence for pairwise colocalization between dementia and stroke, dementia (or AD) and atherosclerosis, and dementia (or AD) and diabetes was found in 2, 6 and 2 genetic regions respectively. Colocalization signals between diabetes and the other 3 non-dementia/AD traits were detected in 5 regions. The colocalization evidence shown in our study suggested shared aetiology between dementia and related diseases such as stroke, atherosclerosis, and diabetes.

Keywords: Alzheimer's disease; Bayesian colocalization; Dementia; Genetics; Multimorbidity; Shared aetiology.