Genetic architecture of epigenetic cortical clock age in brain tissue from older individuals: alterations in

Francine Grodstein, Bernardo Lemos, Jingyun Yang, Katia de Paiva Lopes, Ricardo A Vialle, Nicholas Seyfried, Yanling Wang, Gemma Shireby, Eilis Hannon, Alan Thomas, Keeley Brookes, Jonathan Mill, Philip L De Jager, David A Bennett

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA. · pubmed

Paper

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 (

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Research summary

The paper investigates the genetic architecture of the epigenetic cortical clock, which is related to brain aging. While it provides insights into the mechanisms underlying aging, it primarily focuses on associations rather than addressing root causes or interventions for aging itself. Thus, it contributes to the understanding of aging but does not significantly advance the field in a transformative way.

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