Assessing the co-variability of DNA methylation across peripheral cells and tissues: Implications for the interpretation of findings in epigenetic epidemiology


Autoři: Eilis Hannon aff001;  Georgina Mansell aff001;  Emma Walker aff001;  Marta F. Nabais aff001;  Joe Burrage aff001;  Agnieszka Kepa aff003;  Janis Best-Lane aff004;  Anna Rose aff006;  Suzanne Heck aff007;  Terrie E. Moffitt aff003;  Avshalom Caspi aff003;  Louise Arseneault aff003;  Jonathan Mill aff001
Působiště autorů: University of Exeter Medical School, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom aff001;  Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia aff002;  Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom aff003;  Section of Anaesthetics, Pain Medicine and Intensive Care Medicine, Department of Surgery and Cancer, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom aff004;  Imperial Clinical Trials Unit, Imperial College London, London, United Kingdom aff005;  BRC Flow Cytometry Platform, NIHR GSTT/KCL Comprehensive Biomedical Research Centre, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom aff006;  Biomedical Research Centre at Guy’s and St Thomas’ Hospitals and King’s College London, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom aff007;  Department of Psychology and Neuroscience, Duke University, Durham, United States of America aff008;  Center for Genomic and Computational Biology, Duke University, Durham, United States of America aff009;  Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, United States of America aff010
Vyšlo v časopise: Assessing the co-variability of DNA methylation across peripheral cells and tissues: Implications for the interpretation of findings in epigenetic epidemiology. PLoS Genet 17(3): e1009443. doi:10.1371/journal.pgen.1009443
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1009443

Souhrn

Most epigenome-wide association studies (EWAS) quantify DNA methylation (DNAm) in peripheral tissues such as whole blood to identify positions in the genome where variation is statistically associated with a trait or exposure. As whole blood comprises a mix of cell types, it is unclear whether trait-associated DNAm variation is specific to an individual cellular population. We collected three peripheral tissues (whole blood, buccal epithelial and nasal epithelial cells) from thirty individuals. Whole blood samples were subsequently processed using fluorescence-activated cell sorting (FACS) to purify five constituent cell-types (monocytes, granulocytes, CD4+ T cells, CD8+ T cells, and B cells). DNAm was profiled in all eight sample-types from each individual using the Illumina EPIC array. We identified significant differences in both the level and variability of DNAm between different sample types, and DNAm data-derived estimates of age and smoking were found to differ dramatically across sample types from the same individual. We found that for the majority of loci variation in DNAm in individual blood cell types was only weakly predictive of variance in DNAm measured in whole blood, although the proportion of variance explained was greater than that explained by either buccal or nasal epithelial samples. Covariation across sample types was much higher for DNAm sites influenced by genetic factors. Overall, we observe that DNAm variation in whole blood is additively influenced by a combination of the major blood cell types. For a subset of sites, however, variable DNAm detected in whole blood can be attributed to variation in a single blood cell type providing potential mechanistic insight about EWAS findings. Our results suggest that associations between whole blood DNAm and traits or exposures reflect differences in multiple cell types and our data will facilitate the interpretation of findings in epigenetic epidemiology.

Klíčová slova:

Blood – Blood cells – Cytotoxic T cells – DNA methylation – Epigenetics – Epithelial cells – Granulocytes – T cells


Zdroje

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