Age and mortality associated DNA methylation patterns on the X-chromosome in male and female samples

Li, S.; Lund, J. B.; Baumbach, J.; Christensen, K.; Mengel-From, J.; Li, W.; Mohammadnejad, A.; Pattie, A.; Marioni, R. E.; Deary, I. J.; Tan, Q.

doi:10.1101/636597

bioRxiv · 10.1101/636597

Age and mortality associated DNA methylation patterns on the X-chromosome in male and female samples

Li, S.·Lund, J. B.·Baumbach, J.·Christensen, K.·Mengel-From, J.·Li, W.·Mohammadnejad, A.·Pattie, A.·Marioni, R. E.·Deary, I. J.·Tan, Q.

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Abstract

BackgroundMultiple epigenetic association studies on human aging have been performed reporting large numbers of sites differentially methylated across ages on the autosomal chromosomes. The X-chromosome has been studied little, due to analytical difficulties in dealing with sex differences in X-chromosome content and X-inactivation in females. Based on large collections of genome-wide DNA methylation data on two Danish cohorts of identical twins (mean ages, 66 and 79 years) and the Lothian Birth Cohort 1921 (mean age 79 years), we conducted a chromosome-wide association analysis on male and female samples separately with equal sample sizes to discover age-dependent X-linked DNA methylation patterns using chromosome 20 with about same number of CpGs analysed as an autosomal reference, and compare the age-related changes in DNA methylation between the two sexes. In addition, age-related methylation sites were assessed for their associations with mortality.\n\nResultsWe identified more age-related DNA methylation sites (FDR<0.05) in females than in males. Among them, predominantly more sites were hypermethylated in the older as compared with the younger cohorts, a pattern similar to that observed on chromosome 20. Among the age-related sites, 13 CpGs in males and 24 CpGs in females were found significant (FDR<0.05) in all cohorts. Survival analysis showed that there are more age-methylated CpGs that contribute to reduce mortality than those that increase mortality in male but not in female samples.\n\nConclusionThe X-chromosome displays significant age-and sex-dependent methylation patterns which might be differentially associated with mortality in the two sexes.

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Li, S., Lund, J. B., Baumbach, J., Christensen, K., Mengel-From, J., Li, W., Mohammadnejad, A., Pattie, A., Marioni, R. E., Deary, I. J., Tan, Q.. 2019-05-14. Age and mortality associated DNA methylation patterns on the X-chromosome in male and female samples. https://doi.org/10.1101/636597

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