rs12053868

Carriers of the G allele of rs12053868 accumulated more amyloid as measured by PET scanning and were associated with accelerated cognitive decline in a GWAS of older adults (70+ years of age) compared to non-carriers. This result was confirmed in independent cohorts. Additional findings included: * No significant interactions were identified between rs12053868 and APOE ε4 status, baseline diagnosis, or age or gender; * The association of rs12053868 was genome-wide significant under both additive (P = 1.38 × 10−9) and dominant (P = 5.26 × 10−9) genetic models; * Controlling for age, gender, and TSPO rs6971 genotype, rs12053868(G) was associated with lower cortical microglial activation (P = 0.031); * Using structural MRI in a subset of the GWAS sample (n = 358), rs12053868(G) carriers exhibited greater declines in temporal cortex thickness compared to non-carriers (P = 0.035). This effect remained significant - but just barely - (P = 0.042) after the inclusion of diagnosis as an independent predictor variable. * Of 269 GWAS participants diagnosed with MCI at baseline who had diagnosis information at 2-year follow-up (incl. 42 who progressed to Alzheimer's Disease and 227 who did not), rs12053868(G) carriers were more likely to convert to Alzheimer’s disease within the follow-up period than non-carriers (P = 0.025, odds ratio 2.32, CI:1.11–4.87); * A meta-analysis of 579 participants from three independent cohorts showed that rs12053868(G) was associated with faster 2-year decline in verbal episodic memory performance (P = 7.72 × 10−4), with each copy of the G allele adding approximately one-quarter of a standard deviation to the rate of decline.

A;G

see discussion at rs12053868

G;G

see discussion at rs12053868