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.

中文翻译：

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老年男性 Y 染色体上年龄依赖性 DNA 甲基化模式。


Y染色体是一种仅存在于男性中的性染色体，但由于多种原因在传统的表观遗传关联研究中被忽视。然而，衰老相关表型和死亡率的性别差异可能表明性染色体在衰老过程中发挥着关键作用。我们获得了来自四个队列的 624 名男性 Y 染色体上基于血液的 DNA 甲基化数据，并进行了全染色体表观遗传关联分析，以检测随着年龄的增长而差异甲基化的 Y 连锁 CpG，并交叉验证了四个队列中的显着 CpG。我们确定了 40-219 个显着的 CpG 位点（错误发现率 <0 id=13>82%，其中随着年龄的增长而高度甲基化，这与常染色体报告的模式形成鲜明对比。比较 Y- 的变化率代表不同年龄区间的队列之间的连锁 DNA 甲基化揭示了随着年龄的增长，DNA 甲基化加速的趋势。进一步检查了 Y 染色体上的年龄依赖性 DNA 甲基化模式与全因死亡率的关系，结果表明， Y 染色体上与年龄相关的高甲基化模式与死亡风险降低相关。