Epigenetic findings in periodontitis in UK twins: a cross-sectional study
Epigenetic findings in periodontitis in UK twins: a cross-sectional study
Background: genetic and environmental risk factors contribute to periodontal disease, but the underlying susceptibility pathways are not fully understood. Epigenetic mechanisms are malleable regulators of gene function that can change in response to genetic and environmental stimuli, thereby providing a potential mechanism for mediating risk effects in periodontitis. The aim of this study is to identify epigenetic changes across tissues that are associated with periodontal disease.
Methods: self-reported gingival bleeding and history of gum disease, or tooth mobility, were used as indicators of periodontal disease. DNA methylation profiles were generated using the Infinium HumanMethylation450 BeadChip in whole blood, buccal, and adipose tissue samples from predominantly older female twins (mean age 58) from the TwinsUK cohort. Epigenome-wide association scans (EWAS) of gingival bleeding and tooth mobility were conducted in whole blood in 528 and 492 twins, respectively. Subsequently, targeted candidate gene analysis at 28 genomic regions was carried out testing for phenotype-methylation associations in 41 (tooth mobility) and 43 (gingival bleeding) buccal, and 501 (tooth mobility) and 556 (gingival bleeding) adipose DNA samples.
Results: epigenome-wide analyses in blood identified one CpG-site (cg21245277 in ZNF804A) associated with gingival bleeding (FDR = 0.03, nominal p value = 7.17e-8) and 58 sites associated with tooth mobility (FDR < 0.05) with the top signals in IQCE and XKR6. Epigenetic variation at 28 candidate regions (247 CpG-sites) for chronic periodontitis showed an enrichment for association with periodontal traits, and signals in eight genes (VDR, IL6ST, TMCO6, IL1RN, CD44, IL1B, WHAMM, and CXCL1) were significant in both traits. The methylation-phenotype association signals validated in buccal samples, and a subset (25%) also validated in adipose tissue.
Conclusions: epigenome-wide analyses in adult female twins identified specific DNA methylation changes linked to self-reported periodontal disease. Future work will explore the environmental basis and functional impact of these results to infer potential for strategic personalized treatments and prevention of chronic periodontitis.
DNA methylation, Epigenetics, Epigenome-wide association scan (EWAS), Gene expression, Metabolomics, Periodontitis
Kurushima, Yuko
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Tsai, Pei Chien
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Castillo-Fernandez, Juan
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Couto Alves, Alexessander
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El-Sayed Moustafa, Julia Sarah
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Le Roy, Caroline
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Spector, Tim D.
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Ide, Mark
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Hughes, Francis J.
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Small, Kerrin S.
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Steves, Claire J.
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Bell, Jordana T.
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13 February 2019
Kurushima, Yuko
47554c91-40ac-4f07-8a43-cdf3b2a47d23
Tsai, Pei Chien
9d432618-bfaa-4bb6-af5e-08560ee6885c
Castillo-Fernandez, Juan
f7fe3132-18fb-4910-b51d-540859729a1c
Couto Alves, Alexessander
87b9179e-abde-4ca5-abfc-4b7c5ac8b03b
El-Sayed Moustafa, Julia Sarah
cffd76c8-c36b-4b12-968e-8917148d54d7
Le Roy, Caroline
dd9be377-3200-49be-b8d1-209160d2be0f
Spector, Tim D.
965dbeb9-fc69-4283-b1a3-3aa1fcd38e96
Ide, Mark
aa4a27a1-7c6b-491c-a42d-16337a8d0c11
Hughes, Francis J.
ded7cfa8-ac88-4acf-9625-d127eed35397
Small, Kerrin S.
44cccbd3-4bcb-4526-a518-c554915bcb85
Steves, Claire J.
ca1a35c9-7379-4af2-93e2-e2c78a008dab
Bell, Jordana T.
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Kurushima, Yuko, Tsai, Pei Chien, Castillo-Fernandez, Juan, Couto Alves, Alexessander, El-Sayed Moustafa, Julia Sarah, Le Roy, Caroline, Spector, Tim D., Ide, Mark, Hughes, Francis J., Small, Kerrin S., Steves, Claire J. and Bell, Jordana T.
(2019)
Epigenetic findings in periodontitis in UK twins: a cross-sectional study.
Clinical Epigenetics, 11 (1), [27].
(doi:10.1186/s13148-019-0614-4).
Abstract
Background: genetic and environmental risk factors contribute to periodontal disease, but the underlying susceptibility pathways are not fully understood. Epigenetic mechanisms are malleable regulators of gene function that can change in response to genetic and environmental stimuli, thereby providing a potential mechanism for mediating risk effects in periodontitis. The aim of this study is to identify epigenetic changes across tissues that are associated with periodontal disease.
Methods: self-reported gingival bleeding and history of gum disease, or tooth mobility, were used as indicators of periodontal disease. DNA methylation profiles were generated using the Infinium HumanMethylation450 BeadChip in whole blood, buccal, and adipose tissue samples from predominantly older female twins (mean age 58) from the TwinsUK cohort. Epigenome-wide association scans (EWAS) of gingival bleeding and tooth mobility were conducted in whole blood in 528 and 492 twins, respectively. Subsequently, targeted candidate gene analysis at 28 genomic regions was carried out testing for phenotype-methylation associations in 41 (tooth mobility) and 43 (gingival bleeding) buccal, and 501 (tooth mobility) and 556 (gingival bleeding) adipose DNA samples.
Results: epigenome-wide analyses in blood identified one CpG-site (cg21245277 in ZNF804A) associated with gingival bleeding (FDR = 0.03, nominal p value = 7.17e-8) and 58 sites associated with tooth mobility (FDR < 0.05) with the top signals in IQCE and XKR6. Epigenetic variation at 28 candidate regions (247 CpG-sites) for chronic periodontitis showed an enrichment for association with periodontal traits, and signals in eight genes (VDR, IL6ST, TMCO6, IL1RN, CD44, IL1B, WHAMM, and CXCL1) were significant in both traits. The methylation-phenotype association signals validated in buccal samples, and a subset (25%) also validated in adipose tissue.
Conclusions: epigenome-wide analyses in adult female twins identified specific DNA methylation changes linked to self-reported periodontal disease. Future work will explore the environmental basis and functional impact of these results to infer potential for strategic personalized treatments and prevention of chronic periodontitis.
Text
s13148-019-0614-4
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Accepted/In Press date: 11 January 2019
e-pub ahead of print date: 13 February 2019
Published date: 13 February 2019
Keywords:
DNA methylation, Epigenetics, Epigenome-wide association scan (EWAS), Gene expression, Metabolomics, Periodontitis
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Local EPrints ID: 509395
URI: http://eprints.soton.ac.uk/id/eprint/509395
ISSN: 1868-7075
PURE UUID: 533d4d2b-48a8-41f8-8279-b1149d0b4408
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Date deposited: 20 Feb 2026 17:33
Last modified: 21 Feb 2026 03:20
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Contributors
Author:
Yuko Kurushima
Author:
Pei Chien Tsai
Author:
Juan Castillo-Fernandez
Author:
Alexessander Couto Alves
Author:
Julia Sarah El-Sayed Moustafa
Author:
Caroline Le Roy
Author:
Tim D. Spector
Author:
Mark Ide
Author:
Francis J. Hughes
Author:
Kerrin S. Small
Author:
Claire J. Steves
Author:
Jordana T. Bell
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