A large candidate-gene association study suggests genetic variants at IRF5 and PRDM1 to be associated with aggressive periodontitis

A.S. Schaefer; A. Jochens; H. Dommisch; C. Graetz; Y. Jockel-Schneider; I. Harks; I. Staufenbiel; J. Meyle; P. Eickholz; M. Folwaczny; M. Laine; B. Noack; C. Wijmenga; W. Lieb; C. Bruckmann; S. Schreiber; S. Jepsen; B.G. Loos

doi:10.1111/jcpe.12314

A large candidate-gene association study suggests genetic variants at IRF5 and PRDM1 to be associated with aggressive periodontitis

A.S. Schaefer, A. Jochens, H. Dommisch, C. Graetz, Y. Jockel-Schneider, I. Harks, I. Staufenbiel, J. Meyle, P. Eickholz, M. Folwaczny, M. Laine, B. Noack, C. Wijmenga, W. Lieb, C. Bruckmann, S. Schreiber, S. Jepsen, B.G. Loos

Periodontology

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Aim
Epidemiological and clinical studies indicated a relationship of periodontitis with rheumatoid arthritis (RA). We aimed to identify shared genetic susceptibility loci of RA and periodontitis.

Materials and Methods
Forty-seven risk genes of genome-wide significance of RA and SLE were genotyped in a German case-control sample of aggressive periodontitis (AgP), using Immunochip genotyping arrays (Illumina, 600 cases, 1440 controls) and Affymetrix 500 K Genotyping Arrays (280 cases and 983 controls). Significant associations were replicated in 168 Dutch AgP cases and 679 controls and adjusted for the confounders smoking and sex.

Results
Variants at IRF5 and PRDM1 showed association with AgP. Upon covariate adjustment for smoking and sex, the most strongly associated variant at IRF5 was the rare variant rs62481981 (ppooled = 0.0012, odds ratio [OR] = 3.1, 95% confidence interval [95% CI] = 1.6-6.1; 801 cases, 1476 controls).Within PRDM1 it was rs6923419 (ppooled = 0.004, OR = 0.7, 95% CI = 0.6-0.9; 833 cases, 1440 controls). The associations lost significance after correction for multiple testing in the replication. Both genes are implicated in beta-interferon signalling and are also genome-wide associated with SLE and inflammatory bowel disease.

Conclusion
The study gives no definite evidence for a pathogenic genetic link of periodontitis and RA but suggests IRF5 and PRDM1 as shared susceptibility factors.

Original language	English
Pages (from-to)	1122-1131
Journal	Journal of Clinical Periodontology
Volume	41
Issue number	12
DOIs	https://doi.org/10.1111/jcpe.12314
Publication status	Published - 2014

Bibliographical note

With supporting information

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10.1111/jcpe.12314

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Schaefer, A. S., Jochens, A., Dommisch, H., Graetz, C., Jockel-Schneider, Y., Harks, I., Staufenbiel, I., Meyle, J., Eickholz, P., Folwaczny, M., Laine, M., Noack, B., Wijmenga, C., Lieb, W., Bruckmann, C., Schreiber, S., Jepsen, S., & Loos, B. G. (2014). A large candidate-gene association study suggests genetic variants at IRF5 and PRDM1 to be associated with aggressive periodontitis. Journal of Clinical Periodontology, 41(12), 1122-1131. https://doi.org/10.1111/jcpe.12314

@article{37fad07a116543a5a8aa3a771dd0a6bc,

title = "A large candidate-gene association study suggests genetic variants at IRF5 and PRDM1 to be associated with aggressive periodontitis",

abstract = "AimEpidemiological and clinical studies indicated a relationship of periodontitis with rheumatoid arthritis (RA). We aimed to identify shared genetic susceptibility loci of RA and periodontitis.Materials and MethodsForty-seven risk genes of genome-wide significance of RA and SLE were genotyped in a German case-control sample of aggressive periodontitis (AgP), using Immunochip genotyping arrays (Illumina, 600 cases, 1440 controls) and Affymetrix 500 K Genotyping Arrays (280 cases and 983 controls). Significant associations were replicated in 168 Dutch AgP cases and 679 controls and adjusted for the confounders smoking and sex.ResultsVariants at IRF5 and PRDM1 showed association with AgP. Upon covariate adjustment for smoking and sex, the most strongly associated variant at IRF5 was the rare variant rs62481981 (ppooled = 0.0012, odds ratio [OR] = 3.1, 95% confidence interval [95% CI] = 1.6-6.1; 801 cases, 1476 controls).Within PRDM1 it was rs6923419 (ppooled = 0.004, OR = 0.7, 95% CI = 0.6-0.9; 833 cases, 1440 controls). The associations lost significance after correction for multiple testing in the replication. Both genes are implicated in beta-interferon signalling and are also genome-wide associated with SLE and inflammatory bowel disease.ConclusionThe study gives no definite evidence for a pathogenic genetic link of periodontitis and RA but suggests IRF5 and PRDM1 as shared susceptibility factors.",

author = "A.S. Schaefer and A. Jochens and H. Dommisch and C. Graetz and Y. Jockel-Schneider and I. Harks and I. Staufenbiel and J. Meyle and P. Eickholz and M. Folwaczny and M. Laine and B. Noack and C. Wijmenga and W. Lieb and C. Bruckmann and S. Schreiber and S. Jepsen and B.G. Loos",

note = "With supporting information",

year = "2014",

doi = "10.1111/jcpe.12314",

language = "English",

volume = "41",

pages = "1122--1131",

journal = "Journal of Clinical Periodontology",

issn = "0303-6979",

publisher = "Blackwell Munksgaard",

number = "12",

}

Schaefer, AS, Jochens, A, Dommisch, H, Graetz, C, Jockel-Schneider, Y, Harks, I, Staufenbiel, I, Meyle, J, Eickholz, P, Folwaczny, M, Laine, M, Noack, B, Wijmenga, C, Lieb, W, Bruckmann, C, Schreiber, S, Jepsen, S & Loos, BG 2014, 'A large candidate-gene association study suggests genetic variants at IRF5 and PRDM1 to be associated with aggressive periodontitis', Journal of Clinical Periodontology, vol. 41, no. 12, pp. 1122-1131. https://doi.org/10.1111/jcpe.12314

TY - JOUR

T1 - A large candidate-gene association study suggests genetic variants at IRF5 and PRDM1 to be associated with aggressive periodontitis

AU - Schaefer, A.S.

AU - Jochens, A.

AU - Dommisch, H.

AU - Graetz, C.

AU - Jockel-Schneider, Y.

AU - Harks, I.

AU - Staufenbiel, I.

AU - Meyle, J.

AU - Eickholz, P.

AU - Folwaczny, M.

AU - Laine, M.

AU - Noack, B.

AU - Wijmenga, C.

AU - Lieb, W.

AU - Bruckmann, C.

AU - Schreiber, S.

AU - Jepsen, S.

AU - Loos, B.G.

N1 - With supporting information

PY - 2014

Y1 - 2014

N2 - AimEpidemiological and clinical studies indicated a relationship of periodontitis with rheumatoid arthritis (RA). We aimed to identify shared genetic susceptibility loci of RA and periodontitis.Materials and MethodsForty-seven risk genes of genome-wide significance of RA and SLE were genotyped in a German case-control sample of aggressive periodontitis (AgP), using Immunochip genotyping arrays (Illumina, 600 cases, 1440 controls) and Affymetrix 500 K Genotyping Arrays (280 cases and 983 controls). Significant associations were replicated in 168 Dutch AgP cases and 679 controls and adjusted for the confounders smoking and sex.ResultsVariants at IRF5 and PRDM1 showed association with AgP. Upon covariate adjustment for smoking and sex, the most strongly associated variant at IRF5 was the rare variant rs62481981 (ppooled = 0.0012, odds ratio [OR] = 3.1, 95% confidence interval [95% CI] = 1.6-6.1; 801 cases, 1476 controls).Within PRDM1 it was rs6923419 (ppooled = 0.004, OR = 0.7, 95% CI = 0.6-0.9; 833 cases, 1440 controls). The associations lost significance after correction for multiple testing in the replication. Both genes are implicated in beta-interferon signalling and are also genome-wide associated with SLE and inflammatory bowel disease.ConclusionThe study gives no definite evidence for a pathogenic genetic link of periodontitis and RA but suggests IRF5 and PRDM1 as shared susceptibility factors.

AB - AimEpidemiological and clinical studies indicated a relationship of periodontitis with rheumatoid arthritis (RA). We aimed to identify shared genetic susceptibility loci of RA and periodontitis.Materials and MethodsForty-seven risk genes of genome-wide significance of RA and SLE were genotyped in a German case-control sample of aggressive periodontitis (AgP), using Immunochip genotyping arrays (Illumina, 600 cases, 1440 controls) and Affymetrix 500 K Genotyping Arrays (280 cases and 983 controls). Significant associations were replicated in 168 Dutch AgP cases and 679 controls and adjusted for the confounders smoking and sex.ResultsVariants at IRF5 and PRDM1 showed association with AgP. Upon covariate adjustment for smoking and sex, the most strongly associated variant at IRF5 was the rare variant rs62481981 (ppooled = 0.0012, odds ratio [OR] = 3.1, 95% confidence interval [95% CI] = 1.6-6.1; 801 cases, 1476 controls).Within PRDM1 it was rs6923419 (ppooled = 0.004, OR = 0.7, 95% CI = 0.6-0.9; 833 cases, 1440 controls). The associations lost significance after correction for multiple testing in the replication. Both genes are implicated in beta-interferon signalling and are also genome-wide associated with SLE and inflammatory bowel disease.ConclusionThe study gives no definite evidence for a pathogenic genetic link of periodontitis and RA but suggests IRF5 and PRDM1 as shared susceptibility factors.

U2 - 10.1111/jcpe.12314

DO - 10.1111/jcpe.12314

M3 - Article

SN - 0303-6979

VL - 41

SP - 1122

EP - 1131

JO - Journal of Clinical Periodontology

JF - Journal of Clinical Periodontology

IS - 12

ER -

A large candidate-gene association study suggests genetic variants at IRF5 and PRDM1 to be associated with aggressive periodontitis

Abstract

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