Combining post-mortem and neuroimaging measures of brain amyloidosis to accelerate genomic discovery - PubMed
3 hours ago
- #Alzheimer's disease
- #genetic covariance
- #GWAS
- The study is the largest GWAS of brain amyloidosis to date, using amyloid PET and postmortem histopathology data from 13,555 individuals of European ancestry.
- It identified three known AD risk loci (BIN1, CR1, APOE) and a novel variant on chromosome 17 (rs35635959) associated with brain amyloidosis.
- Fine-mapping prioritized rs35635959 as a lead variant and an eQTL for TUBG2, with decreased TUBG2 expression linked to increased Aβ burden and AD.
- The study found a modest genetic covariance between amyloid PET and postmortem measures, persisting even after excluding APOE region variants.
- Results demonstrate the power of combining compatible AD endophenotypes to uncover new genetic insights into Alzheimer's disease pathology.