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

Jesper B Lund, Shuxia Li, Kaare Christensen, Jonas Mengel-From, Mette Sørensen Thinggaard, Riccardo E Marioni, John Starr, Alison Pattie, Ian J. Deary, Jan Baumbach, Qihua Tan*

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Resumé

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.
OriginalsprogEngelsk
TidsskriftAging Cell
Antal sider8
ISSN1474-9718
DOI
StatusE-pub ahead of print - 2019

Fingeraftryk

DNA Methylation
Epigenomics
Sex Characteristics

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title = "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.",
keywords = "DNA mathylation, Y chromosome, age-dependent patterns, aging, mortality",
author = "Lund, {Jesper B} and Shuxia Li and Kaare Christensen and Jonas Mengel-From and Thinggaard, {Mette S{\o}rensen} and Marioni, {Riccardo E} and John Starr and Alison Pattie and Deary, {Ian J.} and Jan Baumbach and Qihua Tan",
year = "2019",
doi = "10.1111/acel.12907",
language = "English",
journal = "Aging Cell",
issn = "1474-9718",
publisher = "Wiley-Blackwell",

}

Age‐dependent DNA methylation patterns on the Y chromosome in elderly males. / Lund, Jesper B; Li, Shuxia; Christensen, Kaare; Mengel-From, Jonas; Thinggaard, Mette Sørensen; Marioni, Riccardo E; Starr, John ; Pattie, Alison ; Deary, Ian J. ; Baumbach, Jan; Tan, Qihua.

I: Aging Cell, 2019.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Age‐dependent DNA methylation patterns on the Y chromosome in elderly males

AU - Lund, Jesper B

AU - Li, Shuxia

AU - Christensen, Kaare

AU - Mengel-From, Jonas

AU - Thinggaard, Mette Sørensen

AU - Marioni, Riccardo E

AU - Starr, John

AU - Pattie, Alison

AU - Deary, Ian J.

AU - Baumbach, Jan

AU - Tan, Qihua

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - DNA mathylation

KW - Y chromosome

KW - age-dependent patterns

KW - aging

KW - mortality

U2 - 10.1111/acel.12907

DO - 10.1111/acel.12907

M3 - Journal article

JO - Aging Cell

JF - Aging Cell

SN - 1474-9718

ER -