Concordant and discordant DNA methylation signatures of aging in human blood and brain

被引：107

作者：

Farre, Pau ^{[1
]}

Jones, Meaghan J. ^{[2
,3
]}

Meaney, Michael J. ^{[4
,5
,6
]}

Emberly, Eldon ^{[1
]}

Turecki, Gustavo ^{[7
]}

Kobor, Michael S. ^{[2
,3
,6
]}

机构：

[1] Simon Fraser Univ, Dept Phys, Burnaby, BC V5A 1S6, Canada

[2] Child & Family Res Inst, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 4H4, Canada

[3] Univ British Columbia, Dept Med Genet, Vancouver, BC V5Z 4H4, Canada

[4] McGill Univ, Douglas Mental Hlth Univ Inst, Ludmer Ctr Neuroinformat & Mental Hlth, Verdun, PQ H4H 1R3, Canada

[5] Singapore Inst Clin Sci, Singapore 117609, Singapore

[6] Canadian Inst Adv Res, Toronto, ON, Canada

[7] McGill Univ, Dept Psychiat, Verdun, PQ H4H 1R3, Canada

来源：

EPIGENETICS & CHROMATIN | 2015年 / 8卷

基金：

加拿大自然科学与工程研究理事会;

关键词：

DNA methylation; Principal component analysis; Aging; Brain; Blood; Epigenetics; CELLULAR HETEROGENEITY; WIDE; AGE; 5-HYDROXYMETHYLCYTOSINE; 5-METHYLCYTOSINE; TISSUE; CELLS; ANNOTATION; VALIDATION; PROFILES;

D O I：

10.1186/s13072-015-0011-y

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Background: DNA methylation is an epigenetic mark that balances plasticity with stability. While DNA methylation exhibits tissue specificity, it can also vary with age and potentially environmental exposures. In studies of DNA methylation, samples from specific tissues, especially brain, are frequently limited and so surrogate tissues are often used. As yet, we do not fully understand how DNA methylation profiles of these surrogate tissues relate to the profiles of the central tissue of interest. Results: We have adapted principal component analysis to analyze data from the Illumina 450K Human Methylation array using a set of 17 individuals with 3 brain regions and whole blood. All of the top five principal components in our analysis were associated with a variable of interest: principal component 1 (PC1) differentiated brain from blood, PCs 2 and 3 were representative of tissue composition within brain and blood, respectively, and PCs 4 and 5 were associated with age of the individual (PC4 in brain and PC5 in both brain and blood). We validated our age-related PCs in four independent sample sets, including additional brain and blood samples and liver and buccal cells. Gene ontology analysis of all five PCs showed enrichment for processes that inform on the functions of each PC. Conclusions: Principal component analysis (PCA) allows simultaneous and independent analysis of tissue composition and other phenotypes of interest. We discovered an epigenetic signature of age that is not associated with cell type composition and required no correction for cellular heterogeneity.

引用

页数：17

共 56 条

[1] DNA Methylation Analysis in Nonalcoholic Fatty Liver Disease Suggests Distinct Disease-Specific and Remodeling Signatures after Bariatric Surgery [J].

Ahrens, Markus ;

Ammerpohl, Ole ;

von Schoenfels, Witigo ;

Kolarova, Julia ;

Bens, Susanne ;

Itzel, Timo ;

Teufel, Andreas ;

Herrmann, Alexander ;

Brosch, Mario ;

Hinrichsen, Holger ;

Erhart, Wiebke ;

Egberts, Jan ;

Sipos, Bence ;

Schreiber, Stefan ;

Haesler, Robert ;

Stickel, Felix ;

Becker, Thomas ;

Krawczak, Michael ;

Roecken, Christoph ;

Siebert, Reiner ;

Schafmayer, Clemens ;

Hampe, Jochen .

CELL METABOLISM, 2013, 18 (02) :296-302

[2] Methylation QTLs Are Associated with Coordinated Changes in Transcription Factor Binding, Histone Modifications, and Gene Expression Levels [J].

Banovich, Nicholas E. ;

Lan, Xun ;

McVicker, Graham ;

van de Geijn, Bryce ;

Degner, Jacob F. ;

Blischak, John D. ;

Roux, Julien ;

Pritchard, Jonathan K. ;

Gilad, Yoav .

PLOS GENETICS, 2014, 10 (09)

[3] Epigenome-Wide Scans Identify Differentially Methylated Regions for Age and Age-Related Phenotypes in a Healthy Ageing Population [J].

Bell, Jordana T. ;

Tsai, Pei-Chien ;

Yang, Tsun-Po ;

Pidsley, Ruth ;

Nisbet, James ;

Glass, Daniel ;

Mangino, Massimo ;

Zhai, Guangju ;

Zhang, Feng ;

Valdes, Ana ;

Shin, So-Youn ;

Dempster, Emma L. ;

Murray, Robin M. ;

Grundberg, Elin ;

Hedman, Asa K. ;

Nica, Alexandra ;

Small, Kerrin S. ;

Dermitzakis, Emmanouil T. ;

McCarthy, Mark I. ;

Mill, Jonathan ;

Spector, Tim D. ;

Deloukas, Panos .

PLOS GENETICS, 2012, 8 (04) :189-200

[4] Mosaic Epigenetic Dysregulation of Ectodermal Cells in Autism Spectrum Disorder [J].

Berko, Esther R. ;

Suzuki, Masako ;

Beren, Faygel ;

Lemetre, Christophe ;

Alaimo, Christine M. ;

Calder, R. Brent ;

Ballaban-Gil, Karen ;

Gounder, Batya ;

Kampf, Kaylee ;

Kirschen, Jill ;

Maqbool, Shahina B. ;

Momin, Zeineen ;

Reynolds, David M. ;

Russo, Natalie ;

Shulman, Lisa ;

Stasiek, Edyta ;

Tozour, Jessica ;

Valicenti-McDermott, Maria ;

Wang, Shenglong ;

Abrahams, Brett S. ;

Hargitai, Joseph ;

Inbar, Dov ;

Zhang, Zhengdong ;

Buxbaum, Joseph D. ;

Molholm, Sophie ;

Foxe, John J. ;

Marion, Robert W. ;

Auton, Adam ;

Greally, John M. .

PLOS GENETICS, 2014, 10 (05)

[5] An integrated epigenetic and genetic approach to common human disease [J].

Bjornsson, HT ;

Fallin, MD ;

Feinberg, AP .

TRENDS IN GENETICS, 2004, 20 (08) :350-358

[6] The Relationship of DNA Methylation with Age, Gender and Genotype in Twins and Healthy Controls [J].

Boks, Marco P. ;

Derks, Eske M. ;

Weisenberger, Daniel J. ;

Strengman, Erik ;

Janson, Esther ;

Sommer, Iris E. ;

Kahn, Rene S. ;

Ophoff, Roel A. .

PLOS ONE, 2009, 4 (08)

[7] Quantitative Sequencing of 5-Methylcytosine and 5-Hydroxymethylcytosine at Single-Base Resolution [J].

Booth, Michael J. ;

Branco, Miguel R. ;

Ficz, Gabriella ;

Oxley, David ;

Krueger, Felix ;

Reik, Wolf ;

Balasubramanian, Shankar .

SCIENCE, 2012, 336 (6083) :934-937

[8] Aging and Environmental Exposures Alter Tissue-Specific DNA Methylation Dependent upon CpG Island Context [J].

Christensen, Brock C. ;

Houseman, E. Andres ;

Marsit, Carmen J. ;

Zheng, Shichun ;

Wrensch, Margaret R. ;

Wiemels, Joseph L. ;

Nelson, Heather H. ;

Karagas, Margaret R. ;

Padbury, James F. ;

Bueno, Raphael ;

Sugarbaker, David J. ;

Yeh, Ru-Fang ;

Wiencke, John K. ;

Kelsey, Karl T. .

PLOS GENETICS, 2009, 5 (08)

[9] Statistical significance of variables driving systematic variation in high-dimensional data [J].

Chung, Neo Christopher ;

Storey, John D. .

BIOINFORMATICS, 2015, 31 (04) :545-554

[10] Functional annotation of the human brain methylome identifies tissue-specific epigenetic variation across brain and blood [J].

Davies, Matthew N. ;

Volta, Manuela ;

Pidsley, Ruth ;

Lunnon, Katie ;

Dixit, Abhishek ;

Lovestone, Simon ;

Coarfa, Cristian ;

Harris, R. Alan ;

Milosavljevic, Aleksandar ;

Troakes, Claire ;

Al-Sarraj, Safa ;

Dobson, Richard ;

Schalkwyk, Leonard C. ;

Mill, Jonathan .

GENOME BIOLOGY, 2012, 13 (06) :R43

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