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Comprehensive longitudinal study of epigenetic mutations in aging
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
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2019 (English)In: Clinical Epigenetics, E-ISSN 1868-7083, Vol. 11, article id 187Article in journal (Refereed) Published
Abstract [en]

Background: The role of DNA methylation in aging has been widely studied. However, epigenetic mutations, here defined as aberrant methylation levels compared to the distribution in a population, are less understood. Hence, we investigated longitudinal accumulation of epigenetic mutations, using 994 blood samples collected at up to five time points from 375 individuals in old ages.

Results: We verified earlier cross-sectional evidence on the increase of epigenetic mutations with age, and identified important contributing factors including sex, CD19+ B cells, genetic background, cancer diagnosis, and technical artifacts. We further classified epigenetic mutations into High/Low Methylation Outliers (HMO/LMO) according to their changes in methylation, and specifically studied methylation sites (CpGs) that were prone to mutate (frequently mutated CpGs). We validated four epigenetically mutated CpGs using pyrosequencing in 93 samples. Furthermore, by using twins, we concluded that the age-related accumulation of epigenetic mutations was not related to genetic factors, hence driven by stochastic or environmental effects.

Conclusions: Here we conducted a comprehensive study of epigenetic mutation and highlighted its important role in aging process and cancer development. 

Place, publisher, year, edition, pages
BioMed Central, 2019. Vol. 11, article id 187
Keywords [en]
Aging, Cancer, Epigenetic mutation, Twin study, adult, article, artifact, B lymphocyte, cancer diagnosis, epigenetics, female, genetic background, human, human cell, human experiment, human tissue, longitudinal study, major clinical study, male, methylation, pyrosequencing, stochastic model
National Category
Cancer and Oncology Medical Genetics
Identifiers
URN: urn:nbn:se:hj:diva-47209DOI: 10.1186/s13148-019-0788-9PubMedID: 31818313Scopus ID: 2-s2.0-85076285980Local ID: GOA HHJ 2019OAI: oai:DiVA.org:hj-47209DiVA, id: diva2:1382150
Available from: 2020-01-02 Created: 2020-01-02 Last updated: 2020-01-02Bibliographically approved

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Karlsson, Ida K.

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