The effect of age on DNA methylation in whole blood among Bangladeshi men and women

Rick J Jansen, Lin Tong, Maria Argos, Farzana Jasmine, Muhammad Rakibuz-Zaman, Golam Sarwar, Md Tariqul Islam, Hasan Shahriar, Tariqul Islam, Mahfuzar Rahman, Md Yunus, Muhammad G. Kibriya, John A. Baron, Habibul Ahsan, Brandon L. Pierce

Research output: Contribution to journalArticle

Abstract

Background: It is well-known that methylation changes occur as humans age, however, understanding how age-related changes in DNA methylation vary by sex is lacking. In this study, we characterize the effect of age on DNA methylation in a sex-specific manner and determine if these effects vary by genomic context. We used the Illumina HumanMethylation 450 K array and DNA derived from whole blood for 400 adult participants (189 males and 211 females) from Bangladesh to identify age-associated CpG sites and regions and characterize the location of these age-associated sites with respect to CpG islands (vs. shore, shelf, or open sea) and gene regions (vs. intergenic). We conducted a genome-wide search for age-associated CpG sites (among 423,604 sites) using a reference-free approach to adjust for cell type composition (the R package RefFreeEWAS) and performed an independent replication analysis of age-associated CpGs. Results: The number of age-associated CpGs (p < 5 x 10-8) were 986 among men and 3479 among women of which 2027(63.8%) and 572 (64.1%) replicated (using Bonferroni adjusted p < 1.2 × 10-5). For both sexes, age-associated CpG sites were more likely to be hyper-methylated with increasing age (compared to hypo-methylated) and were enriched in CpG islands and promoter regions compared with other locations and all CpGs on the array. Although we observed strong correlation between chronological age and previously-developed epigenetic age models (r ≈ 0.8), among our top (based on lowest p-value) age-associated CpG sites only 12 for males and 44 for females are included in these prediction models, and the median chronological age compared to predicted age was 44 vs. 51.7 in males and 45 vs. 52.1 in females. Conclusions: Our results describe genome-wide features of age-related changes in DNA methylation. The observed associations between age and methylation were generally consistent for both sexes, although the associations tended to be stronger among women. Our population may have unique age-related methylation changes that are not captured in the established methylation-based age prediction model we used, which was developed to be non-tissue-specific.

Original languageEnglish (US)
Article number704
JournalBMC genomics
Volume20
Issue number1
DOIs
StatePublished - Sep 10 2019

Fingerprint

DNA Methylation
Methylation
CpG Islands
Genome
Intergenic DNA
Bangladesh
Oligonucleotide Array Sequence Analysis
Genetic Promoter Regions
Epigenomics
Oceans and Seas
Population
Genes

Keywords

  • Age prediction model
  • Age-associated
  • Cell type adjustment
  • Genome-wide
  • Methylation
  • RefFreeEWAS
  • Sex-specific

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Jansen, R. J., Tong, L., Argos, M., Jasmine, F., Rakibuz-Zaman, M., Sarwar, G., ... Pierce, B. L. (2019). The effect of age on DNA methylation in whole blood among Bangladeshi men and women. BMC genomics, 20(1), [704]. https://doi.org/10.1186/s12864-019-6039-9

The effect of age on DNA methylation in whole blood among Bangladeshi men and women. / Jansen, Rick J; Tong, Lin; Argos, Maria; Jasmine, Farzana; Rakibuz-Zaman, Muhammad; Sarwar, Golam; Islam, Md Tariqul; Shahriar, Hasan; Islam, Tariqul; Rahman, Mahfuzar; Yunus, Md; Kibriya, Muhammad G.; Baron, John A.; Ahsan, Habibul; Pierce, Brandon L.

In: BMC genomics, Vol. 20, No. 1, 704, 10.09.2019.

Research output: Contribution to journalArticle

Jansen, RJ, Tong, L, Argos, M, Jasmine, F, Rakibuz-Zaman, M, Sarwar, G, Islam, MT, Shahriar, H, Islam, T, Rahman, M, Yunus, M, Kibriya, MG, Baron, JA, Ahsan, H & Pierce, BL 2019, 'The effect of age on DNA methylation in whole blood among Bangladeshi men and women', BMC genomics, vol. 20, no. 1, 704. https://doi.org/10.1186/s12864-019-6039-9
Jansen, Rick J ; Tong, Lin ; Argos, Maria ; Jasmine, Farzana ; Rakibuz-Zaman, Muhammad ; Sarwar, Golam ; Islam, Md Tariqul ; Shahriar, Hasan ; Islam, Tariqul ; Rahman, Mahfuzar ; Yunus, Md ; Kibriya, Muhammad G. ; Baron, John A. ; Ahsan, Habibul ; Pierce, Brandon L. / The effect of age on DNA methylation in whole blood among Bangladeshi men and women. In: BMC genomics. 2019 ; Vol. 20, No. 1.
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AU - Sarwar, Golam

AU - Islam, Md Tariqul

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N2 - Background: It is well-known that methylation changes occur as humans age, however, understanding how age-related changes in DNA methylation vary by sex is lacking. In this study, we characterize the effect of age on DNA methylation in a sex-specific manner and determine if these effects vary by genomic context. We used the Illumina HumanMethylation 450 K array and DNA derived from whole blood for 400 adult participants (189 males and 211 females) from Bangladesh to identify age-associated CpG sites and regions and characterize the location of these age-associated sites with respect to CpG islands (vs. shore, shelf, or open sea) and gene regions (vs. intergenic). We conducted a genome-wide search for age-associated CpG sites (among 423,604 sites) using a reference-free approach to adjust for cell type composition (the R package RefFreeEWAS) and performed an independent replication analysis of age-associated CpGs. Results: The number of age-associated CpGs (p < 5 x 10-8) were 986 among men and 3479 among women of which 2027(63.8%) and 572 (64.1%) replicated (using Bonferroni adjusted p < 1.2 × 10-5). For both sexes, age-associated CpG sites were more likely to be hyper-methylated with increasing age (compared to hypo-methylated) and were enriched in CpG islands and promoter regions compared with other locations and all CpGs on the array. Although we observed strong correlation between chronological age and previously-developed epigenetic age models (r ≈ 0.8), among our top (based on lowest p-value) age-associated CpG sites only 12 for males and 44 for females are included in these prediction models, and the median chronological age compared to predicted age was 44 vs. 51.7 in males and 45 vs. 52.1 in females. Conclusions: Our results describe genome-wide features of age-related changes in DNA methylation. The observed associations between age and methylation were generally consistent for both sexes, although the associations tended to be stronger among women. Our population may have unique age-related methylation changes that are not captured in the established methylation-based age prediction model we used, which was developed to be non-tissue-specific.

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