Open Access Highly Accessed Research article

Genetic analysis of DNA methylation and gene expression levels in whole blood of healthy human subjects

Kristel R van Eijk12, Simone de Jong5, Marco PM Boks2, Terry Langeveld1, Fabrice Colas3, Jan H Veldink4, Carolien GF de Kovel1, Esther Janson1, Eric Strengman15, Peter Langfelder6, René S Kahn2, Leonard H van den Berg4, Steve Horvath67 and Roel A Ophoff256*

Author Affiliations

1 Department of Medical Genetics, University Medical Center Utrecht, Utrecht, 3584, CG, The Netherlands

2 Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, 3508, GA, The Netherlands

3 Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, 2300, RC, The Netherlands

4 Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, 3508, GA, The Netherlands

5 Center for Neurobehavioral Genetics, University of California Los Angeles, Box 951761 Gonda #4357C, 695 Charles E. Young Drive, South Los Angeles, CA 90095-1761, USA

6 Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA

7 Department of Biostatistics, School of Public Health, University of California, Los Angeles, CA, 90095, USA

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BMC Genomics 2012, 13:636  doi:10.1186/1471-2164-13-636

Published: 17 November 2012

Additional files

Additional file 1:

Table S1. Comprises two tables that list all significant methylation and expression associations in cis (S1a), and trans (S1b).

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Additional file 2:

Figure S1. Are two figures that show the coefficient and explained variance of associations between methylation and expression.

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Additional file 3:

Table S2. Contains tables with all significant cis mQTLs (S2a) and eQTLs (S2b).

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Additional file 4:

Table S3. Is a table with all LEO results. Combinations that have a LEO score above 0.8 for the model S>M>E are shown in light yellow of which LEO scores above 3 are shown in dark yellow. For the reverse model (S>E>M) combinations with a LEO score above 0.8 are shown in orange. Significant p-values (above 0.01) are coloured in green.

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Additional file 5:

Contains supplementary methods, namely, a more detailed description of Weighted Correlation Network Analysis (WGCNA).

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Additional file 6:

Is an overview of the modules identified in the expression (Table1) and methylation (Table2) data.

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Additional file 7:

Includes a table of continuous module membership kMEi of all expression profiles in all expression modules. Each row in the table corresponds to one gene expression profile. Columns give the gene Entrez idenitifier, module label, and kME and the corresponding (uncorrected) p-values for each module. Expression modules are labelled by E.0, E.1, etc.

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Additional file 8:

Includes a table of continuous module membership kMEi of all methylation profiles in all methylation modules. Each row in the table corresponds to one methylation profile. Columns give the gene Entrez idenitifier, module label, and kME and the corresponding (uncorrected) p-values for each module. Methylation modules are analogously labeled by M.0, M.1, etc.

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Additional file 9:

Shows the overlap of expression and methylation modules. Each row corresponds to an expression module (labelled by the numeric labels, colours and total number of genes in the module, on the left), and each column corresponds to a methylation module (labelled the numeric labels, colours, and total number of genes in the module, at the bottom). Numbers in the table indicate number of genes in the overlap, and the Fisher exact test p-value for the overlap. Only overlaps whose p-value is below 0.05 are shown. The table is coloured such that significant overlaps are coloured in strong red colour. Most overlaps are quite small but some are nevertheless statistically highly significant.

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Additional file 10:

Shows the medianRank statistics for the Module preservation with in (A) preservation of expression modules in methylation data, and in (B) preservation of methylation modules in expression data.

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Additional file 11:

Is a table with the number of excluded samples per step.

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Additional file 12:

Is a clusterplot of all samples together with Hapmap phase 3 populations.

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