Translation of mouse model to human gives insights into periodontitis etiology

A. Nashef; M. Munz; E. Weiss; B.G. Loos; S. Jepsen; N. van der Velde; A.G. Uitterlinden; J. Wellmann; K. Berger; P. Hoffmann; M. Laudes; W. Lieb; A. Franke; H. Dommisch; A. Schäfer; Y. Houri-Haddad; F.A. Iraqi

doi:10.1038/s41598-020-61819-0

Translation of mouse model to human gives insights into periodontitis etiology

A. Nashef, M. Munz, E. Weiss, B.G. Loos, S. Jepsen, N. van der Velde, A.G. Uitterlinden, J. Wellmann, K. Berger, P. Hoffmann, M. Laudes, W. Lieb, A. Franke, H. Dommisch, A. Schäfer, Y. Houri-Haddad, F.A. Iraqi

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

Abstract

To suggest candidate genes involved in periodontitis, we combined gene expression data of periodontal biopsies from Collaborative Cross (CC) mouse lines, with previous reported quantitative trait loci (QTL) in mouse and with human genome-wide association studies (GWAS) associated with periodontitis. Periodontal samples from two susceptible, two resistant and two lines that showed bone formation after periodontal infection were collected during infection and naïve status. Differential expressed genes (DEGs) were analyzed in a case-control and case-only design. After infection, eleven protein-coding genes were significantly stronger expressed in resistant CC lines compared to susceptible ones. Of these, the most upregulated genes were MMP20 (P = 0.001), RSPO4 (P = 0.032), CALB1 (P = 1.06×10⁻⁴), and AMTN (P = 0.05). In addition, human orthologous of candidate genes were tested for their association in a case-controls samples of aggressive (AgP) and chronic (CP) periodontitis (5,095 cases, 9,908 controls). In this analysis, variants at two loci, TTLL11/PTGS1 (rs9695213, P = 5.77×10⁻⁵) and RNASE2 (rs2771342, P = 2.84×10⁻⁵) suggested association with both AgP and CP. In the association analysis with AgP only, the most significant associations were located at the HLA loci HLA-DQH1 (rs9271850, P = 2.52×10⁻¹⁴) and HLA-DPA1 (rs17214512, P = 5.14×10⁻⁵). This study demonstrates the utility of the CC RIL populations as a suitable model to investigate the mechanism of periodontal disease.

Original language	English
Article number	4892
Number of pages	10
Journal	Scientific Reports
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41598-020-61819-0
Publication status	Published - 1 Dec 2020

Funding

We thank Dr. Yuval Nevo, Dr. Sharona Algavish and Dr. Hadar Benimen for the bioinformatics support. There are no competing financial interests in relation to the work described. This work was supported by the German Research Foundation DFG (Deutsche Forschungsgemeinschaft; GZ: SCHA 1582/3-1 and SCHA 1582/4-1), the Israel Science Foundation [grant number 429/09], the US-American National Institute of Health (NIH): RO1-DE022527, UL1-TR001111, and RO1-DE021418, The Federal Ministry of Education and Research (01GR0468), German Migraine & Headache Society (DMKG) and unrestricted grants of equal share from Almirall, Astra Zeneca, Berlin Chemie, Boehringer, Boots Health Care, Glaxo-Smith-Kline, Janssen Cilag, McNeil Pharma, MSD Sharp & Dohme and Pfizer, The Federal Ministry of Research and Education (BMBF, grant no. 01ER0816), the Federal Ministry of Education and Research BMBF (FKZ 0315540A), the Heinz Nixdorf Foundation (Germany), the Federal Ministry of Education and Science and the German Research Council (DFG; Project SI 236/8-1, SI 236/9-1, ER 155/6-1). The German Centre financed Genotyping of the Illumina HumanOmni-1 Quad BeadChips of the HNR subjects for Neurodegenerative Diseases (DZNE), Bonn.

Funders	Funder number
Federal Ministry of Education and Research BMBF	FKZ 0315540A
German Migraine & Headache Society
US-American National Institute of Health
National Institutes of Health	RO1-DE021418, RO1-DE022527, UL1-TR001111
Pfizer
Merck Sharp and Dohme
Deutsche Forschungsgemeinschaft	SCHA 1582/3-1, ER 155/6-1, SCHA 1582/4-1, SI 236/8-1, SI 236/9-1
Bundesministerium für Bildung und Forschung	01ER0816, 01GR0468
Israel Science Foundation	429/09
Federalno Ministarstvo Obrazovanja i Nauke
Deutsche Migräne- und Kopfschmerzgesellschaft e.V.
Heinz Nixdorf Stiftung

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41598-020-61819-0

https://hdl.handle.net/11245.1/1502f184-5817-43c0-88da-7838309ae4a9

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Nashef, A., Munz, M., Weiss, E., Loos, B. G., Jepsen, S., van der Velde, N., Uitterlinden, A. G., Wellmann, J., Berger, K., Hoffmann, P., Laudes, M., Lieb, W., Franke, A., Dommisch, H., Schäfer, A., Houri-Haddad, Y., & Iraqi, F. A. (2020). Translation of mouse model to human gives insights into periodontitis etiology. Scientific Reports, 10(1), Article 4892. https://doi.org/10.1038/s41598-020-61819-0

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abstract = "To suggest candidate genes involved in periodontitis, we combined gene expression data of periodontal biopsies from Collaborative Cross (CC) mouse lines, with previous reported quantitative trait loci (QTL) in mouse and with human genome-wide association studies (GWAS) associated with periodontitis. Periodontal samples from two susceptible, two resistant and two lines that showed bone formation after periodontal infection were collected during infection and na{\"i}ve status. Differential expressed genes (DEGs) were analyzed in a case-control and case-only design. After infection, eleven protein-coding genes were significantly stronger expressed in resistant CC lines compared to susceptible ones. Of these, the most upregulated genes were MMP20 (P = 0.001), RSPO4 (P = 0.032), CALB1 (P = 1.06×10−4), and AMTN (P = 0.05). In addition, human orthologous of candidate genes were tested for their association in a case-controls samples of aggressive (AgP) and chronic (CP) periodontitis (5,095 cases, 9,908 controls). In this analysis, variants at two loci, TTLL11/PTGS1 (rs9695213, P = 5.77×10−5) and RNASE2 (rs2771342, P = 2.84×10−5) suggested association with both AgP and CP. In the association analysis with AgP only, the most significant associations were located at the HLA loci HLA-DQH1 (rs9271850, P = 2.52×10−14) and HLA-DPA1 (rs17214512, P = 5.14×10−5). This study demonstrates the utility of the CC RIL populations as a suitable model to investigate the mechanism of periodontal disease.",

author = "A. Nashef and M. Munz and E. Weiss and B.G. Loos and S. Jepsen and {van der Velde}, N. and A.G. Uitterlinden and J. Wellmann and K. Berger and P. Hoffmann and M. Laudes and W. Lieb and A. Franke and H. Dommisch and A. Sch{\"a}fer and Y. Houri-Haddad and F.A. Iraqi",

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Nashef, A, Munz, M, Weiss, E, Loos, BG, Jepsen, S, van der Velde, N, Uitterlinden, AG, Wellmann, J, Berger, K, Hoffmann, P, Laudes, M, Lieb, W, Franke, A, Dommisch, H, Schäfer, A, Houri-Haddad, Y & Iraqi, FA 2020, 'Translation of mouse model to human gives insights into periodontitis etiology', Scientific Reports, vol. 10, no. 1, 4892. https://doi.org/10.1038/s41598-020-61819-0

TY - JOUR

T1 - Translation of mouse model to human gives insights into periodontitis etiology

AU - Nashef, A.

AU - Munz, M.

AU - Weiss, E.

AU - Loos, B.G.

AU - Jepsen, S.

AU - van der Velde, N.

AU - Uitterlinden, A.G.

AU - Wellmann, J.

AU - Berger, K.

AU - Hoffmann, P.

AU - Laudes, M.

AU - Lieb, W.

AU - Franke, A.

AU - Dommisch, H.

AU - Schäfer, A.

AU - Houri-Haddad, Y.

AU - Iraqi, F.A.

PY - 2020/12/1

Y1 - 2020/12/1

N2 - To suggest candidate genes involved in periodontitis, we combined gene expression data of periodontal biopsies from Collaborative Cross (CC) mouse lines, with previous reported quantitative trait loci (QTL) in mouse and with human genome-wide association studies (GWAS) associated with periodontitis. Periodontal samples from two susceptible, two resistant and two lines that showed bone formation after periodontal infection were collected during infection and naïve status. Differential expressed genes (DEGs) were analyzed in a case-control and case-only design. After infection, eleven protein-coding genes were significantly stronger expressed in resistant CC lines compared to susceptible ones. Of these, the most upregulated genes were MMP20 (P = 0.001), RSPO4 (P = 0.032), CALB1 (P = 1.06×10−4), and AMTN (P = 0.05). In addition, human orthologous of candidate genes were tested for their association in a case-controls samples of aggressive (AgP) and chronic (CP) periodontitis (5,095 cases, 9,908 controls). In this analysis, variants at two loci, TTLL11/PTGS1 (rs9695213, P = 5.77×10−5) and RNASE2 (rs2771342, P = 2.84×10−5) suggested association with both AgP and CP. In the association analysis with AgP only, the most significant associations were located at the HLA loci HLA-DQH1 (rs9271850, P = 2.52×10−14) and HLA-DPA1 (rs17214512, P = 5.14×10−5). This study demonstrates the utility of the CC RIL populations as a suitable model to investigate the mechanism of periodontal disease.

AB - To suggest candidate genes involved in periodontitis, we combined gene expression data of periodontal biopsies from Collaborative Cross (CC) mouse lines, with previous reported quantitative trait loci (QTL) in mouse and with human genome-wide association studies (GWAS) associated with periodontitis. Periodontal samples from two susceptible, two resistant and two lines that showed bone formation after periodontal infection were collected during infection and naïve status. Differential expressed genes (DEGs) were analyzed in a case-control and case-only design. After infection, eleven protein-coding genes were significantly stronger expressed in resistant CC lines compared to susceptible ones. Of these, the most upregulated genes were MMP20 (P = 0.001), RSPO4 (P = 0.032), CALB1 (P = 1.06×10−4), and AMTN (P = 0.05). In addition, human orthologous of candidate genes were tested for their association in a case-controls samples of aggressive (AgP) and chronic (CP) periodontitis (5,095 cases, 9,908 controls). In this analysis, variants at two loci, TTLL11/PTGS1 (rs9695213, P = 5.77×10−5) and RNASE2 (rs2771342, P = 2.84×10−5) suggested association with both AgP and CP. In the association analysis with AgP only, the most significant associations were located at the HLA loci HLA-DQH1 (rs9271850, P = 2.52×10−14) and HLA-DPA1 (rs17214512, P = 5.14×10−5). This study demonstrates the utility of the CC RIL populations as a suitable model to investigate the mechanism of periodontal disease.

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DO - 10.1038/s41598-020-61819-0

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VL - 10

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 4892

ER -

Translation of mouse model to human gives insights into periodontitis etiology

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