Dataset Information

Fine-mapping and replication of EWAS loci harboring putative epigenetic alterations associated with AD neuropathology in a large collection of human brain tissue samples.

ABSTRACT:

Introduction

Our previous epigenome-wide association study (EWAS) of Alzheimer's disease (AD) in human brain identified 71 CpGs associated with AD pathology. However, due to low coverage of the Illumina platform, many important CpGs might have been missed.

Methods

In a large collection of human brain tissue samples (N = 864), we fine-mapped previous EWAS loci by targeted bisulfite sequencing and examined their associations with AD neuropathology. DNA methylation was also linked to gene expression of the same brain cortex.

Results

Our targeted sequencing captured 130 CpGs (∼1.2 kb), 93 of which are novel. Of the 130 CpGs, 57 sites (only 17 included in previous EWAS) and 12 gene regions (e.g., ANK1, BIN1, RHBDF2, SPG7, PODXL) were significantly associated with amyloid load. DNA methylation in some regions was associated with expression of nearby genes.

Discussion

Targeted methylation sequencing can validate previous EWAS loci and discover novel CpGs associated with AD pathology.

SUBMITTER: Palma-Gudiel H

PROVIDER: S-EPMC9922334 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

Fine-mapping and replication of EWAS loci harboring putative epigenetic alterations associated with AD neuropathology in a large collection of human brain tissue samples.

Palma-Gudiel Helena H Yu Lei L Huo Zhiguang Z Yang Jingyun J Wang Yanling Y Gu Tongjun T Gao Cheng C De Jager Philip L PL Jin Peng P Bennett David A DA Zhao Jinying J

Alzheimer's & dementia : the journal of the Alzheimer's Association 20220812 4

<h4>Introduction</h4>Our previous epigenome-wide association study (EWAS) of Alzheimer's disease (AD) in human brain identified 71 CpGs associated with AD pathology. However, due to low coverage of the Illumina platform, many important CpGs might have been missed.<h4>Methods</h4>In a large collection of human brain tissue samples (N = 864), we fine-mapped previous EWAS loci by targeted bisulfite sequencing and examined their associations with AD neuropathology. DNA methylation was also linked to ...[more]

PMID: 35959851

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Dataset Information

Fine-mapping and replication of EWAS loci harboring putative epigenetic alterations associated with AD neuropathology in a large collection of human brain tissue samples.

Introduction

Methods

Results

Discussion

Publications

Fine-mapping and replication of EWAS loci harboring putative epigenetic alterations associated with AD neuropathology in a large collection of human brain tissue samples.

Similar Datasets

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