Genetic architecture of epigenetic cortical clock age in brain tissue from older individuals: alterations in CD46 and other loci.

ABSTRACT: The cortical epigenetic clock was developed in brain tissue as a biomarker of brain aging. As one way to identify mechanisms underlying aging, we conducted a GWAS of cortical age. We leveraged postmortem cortex tissue and genotyping array data from 694 participants of the Rush Memory and Aging Project and Religious Orders Study (ROSMAP; 11000,000 SNPs), and meta-analysed ROSMAP with 522 participants of Brains for Dementia Research (5,000,000 overlapping SNPs). We confirmed results using eQTL (cortical bulk and single nucleus gene expression), cortical protein levels (ROSMAP), and phenome-wide association studies (clinical/neuropathologic phenotypes, ROSMAP). In the meta-analysis, the strongest association was rs4244620 (p = 1.29 × 10^-7), which also exhibited FDR-significa

SUBMITTER: Grodstein F 

PROVIDER: S-EPMC11346548 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature