Dataset Information

Age-dependent DNA methylation patterns on the Y chromosome in elderly males.

ABSTRACT: The Y chromosome, a sex chromosome that only exists in males, has been ignored in traditional epigenetic association studies for multiple reasons. However, sex differences in aging-related phenotypes and mortality could suggest a critical role of the sex chromosomes in the aging process. We obtained blood-based DNA methylation data on the Y chromosome for 624 men from four cohorts and performed a chromosome-wide epigenetic association analysis to detect Y-linked CpGs differentially methylated over age and cross-validated the significant CpGs in the four cohorts. We identified 40-219 significant CpG sites (false discovery rate <0.05) with >82% of them hypermethylated with increasing age, which is in strong contrast to the patterns reported on the autosomal chromosomes. Comparing the rate of change in the Y-linked DNA methylation across cohorts that represent different age intervals revealed a trend of acceleration in DNA methylation with increasing age. The age-dependent DNA methylation patterns on the Y chromosome were further examined for their association with all-cause mortality with results suggesting that the predominant pattern of age-related hypermethylation on the Y chromosome is associated with reduced risk of death.

SUBMITTER: Lund JB

PROVIDER: S-EPMC6996942 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Age-dependent DNA methylation patterns on the Y chromosome in elderly males.

Lund Jesper B JB Li Shuxia S Christensen Kaare K Mengel-From Jonas J Soerensen Mette M Marioni Riccardo E RE Starr John J Pattie Alison A Deary Ian J IJ Baumbach Jan J Tan Qihua Q

Aging cell 20190221 2

The Y chromosome, a sex chromosome that only exists in males, has been ignored in traditional epigenetic association studies for multiple reasons. However, sex differences in aging-related phenotypes and mortality could suggest a critical role of the sex chromosomes in the aging process. We obtained blood-based DNA methylation data on the Y chromosome for 624 men from four cohorts and performed a chromosome-wide epigenetic association analysis to detect Y-linked CpGs differentially methylated ov ...[more]

PMID: 30793472

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Project description:BackgroundAge-related changes in DNA methylation (DNAm) play a critical role in regulating gene expression. However, most epigenome-wide association studies have predominantly focused on individuals of European descent. This study aims to characterize longitudinal changes in DNAm patterns in a cohort of elderly Brazilian participants.MethodsDNAm profiles were collected approximately nine years apart from 23 elderly Brazilian individuals using the Illumina Infinium MethyationEPIC BeadChip. Using mixed-effects models, we examined changes in DNAm patterns using both quantitative age and binary timepoint (e.g., baseline vs. follow-up) as predictors of interest to identify differentially methylated positions (DMPs). Significant DMPs were compared with a list of previously identified age-related DMPs. Differentially methylated regions (DMRs) were also identified using DMRcate. Gene ontology (GO) pathway enrichment analyses were performed to explore the functional significance of identified DMPs and DMRs.ResultsOf the 586,229 autosomal probes included in the differential methylation analyses, 2768 significant (FDR < 0.05) age-associated DMPs (aDMPs) and 2757 significant (FDR < 0.05) timepoint-associated DMPs (tpDMPs) were identified. Of the 2768 aDMPs, 1471 were replicated from previous studies. Of the 1297 non-replicated CpGs, 77.4% were exclusive to the EPIC array. The DMR analyses identified 305 age-associated DMRs (aDMRs) and 372 timepoint-associated DMRs (tpDMRs). Both aDMPs and aDMRs exhibited age-related hypermethylation within CpG islands and promoter regions of the genome, whereas hypomethylation predominantly occurred in interCGI and intergenic regions and introns. The GO enrichment analyses identified several neurological and cognition-related pathways enriched for hypermethylated CpG islands, many of which were mapped near transcription start sites and first exon regions.ConclusionsThis longitudinal study identified age-associated and timepoint-associated DMPs and DMRs in a sample of elderly Brazilians. Most of the non-replicated CpGs were found to be on the new EPIC array, suggesting that more age-related studies using the EPIC array are required to validate these CpGs. The GO pathway enrichment analyses identified age-related enrichment of several gene sets related to cognitive and physical decline in elderly populations. The enrichment of these sites could provide evidence for age-related neurodegeneration and cognitive decline in elderly populations.

Dataset Information

Age-dependent DNA methylation patterns on the Y chromosome in elderly males.

Publications

Age-dependent DNA methylation patterns on the Y chromosome in elderly males.

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