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Series GSE37579 Query DataSets for GSE37579
Status Public on Apr 28, 2012
Title DNA modification study of major depressive disorder: beyond locus-by-locus comparisons.
Organism Homo sapiens
Experiment type Methylation profiling by genome tiling array
Summary Major depressive disorder (MDD) exhibits numerous clinical and molecular features that are consistent with putative epigenetic misregulation. Despite growing interest in epigenetic studies of psychiatric diseases, the methodologies guiding such studies have not been well defined. We performed DNA modification analysis in white blood cells from monozygotic twins discordant for MDD, in brain prefrontal cortex, and germline (sperm) samples from affected individuals and control subjects (total N = 304) using 8.1K CpG island microarrays and fine mapping. In addition to the traditional locus-by-locus comparisons, we explored the potential of new analytical approaches in epigenomic studies. In the microarray experiment, we detected a number of nominally significant DNA modification differences in MDD and validated selected targets using bisulfite pyrosequencing. Some MDD epigenetic changes, however, overlapped across brain, blood, and sperm more often than expected by chance. We also demonstrated that stratification for disease severity and age may increase the statistical power of epimutation detection. Finally, a series of new analytical approaches, such as DNA modification networks and machine-learning algorithms using binary and quantitative depression phenotypes, provided additional insights on the epigenetic contributions to MDD. Mapping epigenetic differences in MDD (and other psychiatric diseases) is a complex task. However, combining traditional and innovative analytical strategies may lead to identification of disease-specific etiopathogenic epimutations.
Overall design We performed DNA methylome analysis on white blood cells from monozygotic twins discordant for depression (n=200), pre-frontal cortex (n=71), and germline samples (n=33) from affected individuals and controls (total n=304). DNA samples were enriched for unmodified fraction of the genome using DNA-modification sensitive restriction enzyme digestion followed by adaptor-mediated PCR. The enriched fractions were labelled with a fluorescent dye (Cy5) and hybridized onto the array with a common reference pool (Cy3) generated from individuals unrelated to this study.
Contributor(s) Oh G, Wang S, Chen Z, Khare T, Tochigi M, Ng C, Yang A, Pal M, Kwan A, Kaminsky Z, Mill J, Heath A, Madden P, Gunasinghe C, Tackett J, Gottesman I, Turecki G, Wray N, Montgomery G, McGuffin P, Martin N, Boomsma D, Kustra R, Petronis A
Citation(s) 25108803
Submission date Apr 25, 2012
Last update date Jul 04, 2016
Contact name Art Petronis
Organization name Centre for Addiction and Mental Health
Department Campbell Family Mental Health Research Institute
Lab Krembil Family Epigenetics Laboratory
Street address 250 College St
City Toronto
State/province Ontario
ZIP/Postal code M5T1R8
Country Canada
Platforms (1)
GPL10342 UHN Microarray Centre Human 8.1K CpG island microarray
Samples (304)
GSM922330 Australian Twin Registry monozygotic twin1a control white blood cells1
GSM922331 Australian Twin Registry monozygotic twin1b depression white blood cells2
GSM922332 Australian Twin Registry monozygotic twin2a control white blood cells3
BioProject PRJNA162437

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE37579_RAW.tar 229.7 Mb (http)(custom) TAR (of GPR)
Processed data included within Sample table

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