Genome-wide peripheral blood leukocyte DNA methylation microarrays identified a single association with inflammatory bowel diseases

R. Alan Harris, Dorottya Nagy-Szakal, Natalia Pedersen, Antone Opekun, Jiri Bronsky, Pia Munkholm, Cathrine Jespersgaard, Paalskytt Andersen, B. Melegh, George Ferry, Tine Jess, Richard Kellermayer

Research output: Contribution to journalArticle

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Abstract

Background: Crohn's disease (CD) and ulcerative colitis (UC) are common forms of inflammatory bowel disease (IBD). Monozygotic (MZ) twin discordance rates and epidemiologic data implicate that environmental changes and epigenetic factors may play a pathogenic role in IBD. DNA methylation (the methylation of cytosines within CpG dinucleotides) is an epigenetic modification, which can respond to environmental influences. We investigated whether DNA methylation might be connected with IBD in peripheral blood leukocyte (PBL) DNA by utilizing genome-wide microarrays. Methods: Two different high-throughput microarray-based methods for genome-wide DNA methylation analysis were employed. First, DNA isolated from MZ twin pairs concordant (CD: 4; UC: 3) and discordant (CD: 4; UC: 7) for IBD was interrogated by a custom-made methylation-specific amplification microarray (MSAM). Second, the recently developed Illumina Infinium HumanMethylation450 BeadChip arrays were used on 48 samples of PBL DNA from discordant MZ twin pairs (CD: 3; UC: 3) and treatment-naive pediatric cases of IBD (CD: 14; UC: 8), as well as controls (n = 14). The microarrays were validated with bisulfite pyrosequencing. Results: The MSAMs did not yield significant IBD associations. The Methylation BeadChip approach identified a single DNA methylation association of IBD at TEPP (testis, prostate and placenta-expressed protein) when DNA isolated selectively from peripheral blood mononuclear cells was analyzed (8.6% increase in methylation between CD and control, FDR = 0.0065). Conclusions: Microarray interrogation of IBD-dependent DNA methylation from PBLs appears to have limited ability to detect significant disease associations. More detailed and/or selective approaches may be useful for the elucidation of connections between the DNA methylome and IBD in the future.

Original languageEnglish
Pages (from-to)2334-2341
Number of pages8
JournalInflammatory Bowel Diseases
Volume18
Issue number12
DOIs
Publication statusPublished - Dec 2012

Fingerprint

DNA Methylation
Oligonucleotide Array Sequence Analysis
Inflammatory Bowel Diseases
Leukocytes
Crohn Disease
Genome
Ulcerative Colitis
Methylation
Monozygotic Twins
DNA
Epigenomics
Cytosine
Placenta
Testis
Prostate
Blood Cells
Pediatrics

Keywords

  • DNA methylation
  • inflammatory bowel disease
  • peripheral blood
  • TEPP
  • twin

ASJC Scopus subject areas

  • Gastroenterology
  • Immunology and Allergy

Cite this

Harris, R. A., Nagy-Szakal, D., Pedersen, N., Opekun, A., Bronsky, J., Munkholm, P., ... Kellermayer, R. (2012). Genome-wide peripheral blood leukocyte DNA methylation microarrays identified a single association with inflammatory bowel diseases. Inflammatory Bowel Diseases, 18(12), 2334-2341. https://doi.org/10.1002/ibd.22956

Genome-wide peripheral blood leukocyte DNA methylation microarrays identified a single association with inflammatory bowel diseases. / Harris, R. Alan; Nagy-Szakal, Dorottya; Pedersen, Natalia; Opekun, Antone; Bronsky, Jiri; Munkholm, Pia; Jespersgaard, Cathrine; Andersen, Paalskytt; Melegh, B.; Ferry, George; Jess, Tine; Kellermayer, Richard.

In: Inflammatory Bowel Diseases, Vol. 18, No. 12, 12.2012, p. 2334-2341.

Research output: Contribution to journalArticle

Harris, RA, Nagy-Szakal, D, Pedersen, N, Opekun, A, Bronsky, J, Munkholm, P, Jespersgaard, C, Andersen, P, Melegh, B, Ferry, G, Jess, T & Kellermayer, R 2012, 'Genome-wide peripheral blood leukocyte DNA methylation microarrays identified a single association with inflammatory bowel diseases', Inflammatory Bowel Diseases, vol. 18, no. 12, pp. 2334-2341. https://doi.org/10.1002/ibd.22956
Harris, R. Alan ; Nagy-Szakal, Dorottya ; Pedersen, Natalia ; Opekun, Antone ; Bronsky, Jiri ; Munkholm, Pia ; Jespersgaard, Cathrine ; Andersen, Paalskytt ; Melegh, B. ; Ferry, George ; Jess, Tine ; Kellermayer, Richard. / Genome-wide peripheral blood leukocyte DNA methylation microarrays identified a single association with inflammatory bowel diseases. In: Inflammatory Bowel Diseases. 2012 ; Vol. 18, No. 12. pp. 2334-2341.
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abstract = "Background: Crohn's disease (CD) and ulcerative colitis (UC) are common forms of inflammatory bowel disease (IBD). Monozygotic (MZ) twin discordance rates and epidemiologic data implicate that environmental changes and epigenetic factors may play a pathogenic role in IBD. DNA methylation (the methylation of cytosines within CpG dinucleotides) is an epigenetic modification, which can respond to environmental influences. We investigated whether DNA methylation might be connected with IBD in peripheral blood leukocyte (PBL) DNA by utilizing genome-wide microarrays. Methods: Two different high-throughput microarray-based methods for genome-wide DNA methylation analysis were employed. First, DNA isolated from MZ twin pairs concordant (CD: 4; UC: 3) and discordant (CD: 4; UC: 7) for IBD was interrogated by a custom-made methylation-specific amplification microarray (MSAM). Second, the recently developed Illumina Infinium HumanMethylation450 BeadChip arrays were used on 48 samples of PBL DNA from discordant MZ twin pairs (CD: 3; UC: 3) and treatment-naive pediatric cases of IBD (CD: 14; UC: 8), as well as controls (n = 14). The microarrays were validated with bisulfite pyrosequencing. Results: The MSAMs did not yield significant IBD associations. The Methylation BeadChip approach identified a single DNA methylation association of IBD at TEPP (testis, prostate and placenta-expressed protein) when DNA isolated selectively from peripheral blood mononuclear cells was analyzed (8.6{\%} increase in methylation between CD and control, FDR = 0.0065). Conclusions: Microarray interrogation of IBD-dependent DNA methylation from PBLs appears to have limited ability to detect significant disease associations. More detailed and/or selective approaches may be useful for the elucidation of connections between the DNA methylome and IBD in the future.",
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AU - Opekun, Antone

AU - Bronsky, Jiri

AU - Munkholm, Pia

AU - Jespersgaard, Cathrine

AU - Andersen, Paalskytt

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AB - Background: Crohn's disease (CD) and ulcerative colitis (UC) are common forms of inflammatory bowel disease (IBD). Monozygotic (MZ) twin discordance rates and epidemiologic data implicate that environmental changes and epigenetic factors may play a pathogenic role in IBD. DNA methylation (the methylation of cytosines within CpG dinucleotides) is an epigenetic modification, which can respond to environmental influences. We investigated whether DNA methylation might be connected with IBD in peripheral blood leukocyte (PBL) DNA by utilizing genome-wide microarrays. Methods: Two different high-throughput microarray-based methods for genome-wide DNA methylation analysis were employed. First, DNA isolated from MZ twin pairs concordant (CD: 4; UC: 3) and discordant (CD: 4; UC: 7) for IBD was interrogated by a custom-made methylation-specific amplification microarray (MSAM). Second, the recently developed Illumina Infinium HumanMethylation450 BeadChip arrays were used on 48 samples of PBL DNA from discordant MZ twin pairs (CD: 3; UC: 3) and treatment-naive pediatric cases of IBD (CD: 14; UC: 8), as well as controls (n = 14). The microarrays were validated with bisulfite pyrosequencing. Results: The MSAMs did not yield significant IBD associations. The Methylation BeadChip approach identified a single DNA methylation association of IBD at TEPP (testis, prostate and placenta-expressed protein) when DNA isolated selectively from peripheral blood mononuclear cells was analyzed (8.6% increase in methylation between CD and control, FDR = 0.0065). Conclusions: Microarray interrogation of IBD-dependent DNA methylation from PBLs appears to have limited ability to detect significant disease associations. More detailed and/or selective approaches may be useful for the elucidation of connections between the DNA methylome and IBD in the future.

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