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Meta-Analysis
. 2022 Mar;21(3):e13563.
doi: 10.1111/acel.13563. Epub 2022 Feb 4.

Age-related DNA methylation on Y chromosome and their associations with total mortality among Chinese males

Guyanan Li  1   2 , Chenming Wang  1 , Xin Guan  1 , Yansen Bai  1 , Yue Feng  1 , Wei Wei  1 , Hua Meng  1 , Ming Fu  1 , Meian He  1 , Xiaomin Zhang  1 , Yanjun Lu  3 , Yong Lin  2   4   5 , Huan Guo  1
Affiliations
Meta-Analysis

Age-related DNA methylation on Y chromosome and their associations with total mortality among Chinese males

Guyanan Li et al. Aging Cell. 2022 Mar.

Abstract

In view of the sex differences in aging-related diseases, sex chromosomes may play a critical role during aging process. This study aimed to identify age-related DNA methylation changes on Y chromosome (ChrY). A two-stage study design was conducted in this study. The discovery stage contained 419 Chinese males, including 205 from the Wuhan-Zhuhai cohort panel, 107 from the coke oven workers panel, and 107 from the Shiyan panel. The validation stage contained 587 Chinese males from the Dongfeng-Tongji sub-cohort. We used the Illumina HumanMethylation BeadChip to determine genome-wide DNA methylation in peripheral blood of the study participants. The associations between age and methylation levels of ChrY CpGs were investigated by using linear regression models with adjustment for potential confounders. Further, associations of age-related ChrY CpGs with all-cause mortality were tested in the validation stage. We identified the significant associations of 41 ChrY CpGs with age at false discovery rate (FDR) <0.05 in the discovery stage, and 18 of them were validated in the validation stage (p < 0.05). Meta-analysis of both stages confirmed the robust positive associations of 14 CpGs and negative associations of 4 CpGs with age (FDR<0.05). Among them, cg03441493 and cg17816615 were significantly associated with all-cause mortality risk [HR(95% CI) = 1.37 (1.04, 1.79) and 0.70 (0.54, 0.93), respectively]. Our results highlighted the importance of ChrY CpGs on male aging.

Keywords: DNA methylation; Y chromosome; aging; mortality.

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Conflict of interest statement

The authors declared no competing interests.

Figures

FIGURE 1
FIGURE 1
Weighted methylation risk score (MRS) on Y chromosome (ChrY) and age among participants. (a) Distribution of age in each study panel. (b) Distribution of weighted MRS on ChrY in each study panel. (c) Association of weighted MRS on ChrY with age. Trend line was fitted by linear regression model. Weighted MRS was calculated as the sum of their coefficients with age multiplied by methylation levels of corresponding CpGs
FIGURE 2
FIGURE 2
Methylation‐expression correlations for age‐related CpGs on ChrY. (a) and (b) correlations of cg13845521 and cg11816202 with the expression level of TTTY14 (probe ILMN_2143383); (c) and (d) correlations of cg01988452 and cg13308744 with the expression level of EIF1AY (probe ILMN_1755537); (e) and (f) correlations of cg01988452 and cg13308744 with the expression level of EIF1AY (probe ILMN_2228976). Only methylation‐expression correlations with p < 0.05 were presented
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