Meta-analysis of genome-wide association studies of aggressive and chronic periodontitis identifies two novel risk loci

Matthias Munz, Gesa M. Richter, Bruno G. Loos, Søren Jepsen, Kimon Divaris, Steven Offenbacher, Alexander Teumer, Birte Holtfreter, Thomas Kocher, Corinna Bruckmann, Yvonne Jockel-Schneider, Christian Graetz, Ilyas Ahmad, Ingmar Staufenbiel, Nathalie Van Der Velde, André G. Uitterlinden, Lisette C.P.G.M. De Groot, Jürgen Wellmann, Klaus Berger, Bastian Krone & 7 others Per Hoffmann, Matthias Laudes, Wolfgang Lieb, Andre Franke, Jeanette Erdmann, Henrik Dommisch, Arne S. Schaefer

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Periodontitis is one of the most common inflammatory diseases, with a prevalence of 11% worldwide for the severe forms and an estimated heritability of 50%. It is classified into the widespread moderate form chronic periodontitis (CP) and the rare early-onset and severe phenotype aggressive periodontitis (AgP). These different disease manifestations are thought to share risk alleles and predisposing environmental factors. To obtain novel insights into the shared genetic etiology and the underlying molecular mechanisms of both forms, we performed a two step-wise meta-analysis approach using genome-wide association studies of both phenotypes. Genotypes from imputed genome-wide association studies (GWAS) of AgP and CP comprising 5,095 cases and 9,908 controls of North-West European genetic background were included. Two loci were associated with periodontitis at a genome-wide significance level. They located within the pseudogene MTND1P5 on chromosome 8 (rs16870060-G, P = 3.69 × 10−9, OR = 1.36, 95% CI = [1.23–1.51]) and intronic of the long intergenic non-coding RNA LOC107984137 on chromosome 16, downstream of the gene SHISA9 (rs729876-T, P = 9.77 × 10−9, OR = 1.24, 95% CI = [1.15–1.34]). This study identified novel risk loci of periodontitis, adding to the genetic basis of AgP and CP.
LanguageEnglish
Pages102-113
JournalEuropean Journal of Human Genetics
Volume27
Issue number1
Early online date14 Sep 2018
DOIs
Publication statusPublished - 2019

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Aggressive Periodontitis
Chronic Periodontitis
Periodontitis
Genome-Wide Association Study
Meta-Analysis
Long Noncoding RNA
Phenotype
Chromosomes, Human, Pair 16
Chromosomes, Human, Pair 8
Pseudogenes
Causality
Alleles
Genotype
Genome
Genes

Cite this

Munz, Matthias ; Richter, Gesa M. ; Loos, Bruno G. ; Jepsen, Søren ; Divaris, Kimon ; Offenbacher, Steven ; Teumer, Alexander ; Holtfreter, Birte ; Kocher, Thomas ; Bruckmann, Corinna ; Jockel-Schneider, Yvonne ; Graetz, Christian ; Ahmad, Ilyas ; Staufenbiel, Ingmar ; Van Der Velde, Nathalie ; Uitterlinden, André G. ; De Groot, Lisette C.P.G.M. ; Wellmann, Jürgen ; Berger, Klaus ; Krone, Bastian ; Hoffmann, Per ; Laudes, Matthias ; Lieb, Wolfgang ; Franke, Andre ; Erdmann, Jeanette ; Dommisch, Henrik ; Schaefer, Arne S. / Meta-analysis of genome-wide association studies of aggressive and chronic periodontitis identifies two novel risk loci. In: European Journal of Human Genetics. 2019 ; Vol. 27, No. 1. pp. 102-113.
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title = "Meta-analysis of genome-wide association studies of aggressive and chronic periodontitis identifies two novel risk loci",
abstract = "Periodontitis is one of the most common inflammatory diseases, with a prevalence of 11{\%} worldwide for the severe forms and an estimated heritability of 50{\%}. It is classified into the widespread moderate form chronic periodontitis (CP) and the rare early-onset and severe phenotype aggressive periodontitis (AgP). These different disease manifestations are thought to share risk alleles and predisposing environmental factors. To obtain novel insights into the shared genetic etiology and the underlying molecular mechanisms of both forms, we performed a two step-wise meta-analysis approach using genome-wide association studies of both phenotypes. Genotypes from imputed genome-wide association studies (GWAS) of AgP and CP comprising 5,095 cases and 9,908 controls of North-West European genetic background were included. Two loci were associated with periodontitis at a genome-wide significance level. They located within the pseudogene MTND1P5 on chromosome 8 (rs16870060-G, P = 3.69 × 10−9, OR = 1.36, 95{\%} CI = [1.23–1.51]) and intronic of the long intergenic non-coding RNA LOC107984137 on chromosome 16, downstream of the gene SHISA9 (rs729876-T, P = 9.77 × 10−9, OR = 1.24, 95{\%} CI = [1.15–1.34]). This study identified novel risk loci of periodontitis, adding to the genetic basis of AgP and CP.",
author = "Matthias Munz and Richter, {Gesa M.} and Loos, {Bruno G.} and S{\o}ren Jepsen and Kimon Divaris and Steven Offenbacher and Alexander Teumer and Birte Holtfreter and Thomas Kocher and Corinna Bruckmann and Yvonne Jockel-Schneider and Christian Graetz and Ilyas Ahmad and Ingmar Staufenbiel and {Van Der Velde}, Nathalie and Uitterlinden, {Andr{\'e} G.} and {De Groot}, {Lisette C.P.G.M.} and J{\"u}rgen Wellmann and Klaus Berger and Bastian Krone and Per Hoffmann and Matthias Laudes and Wolfgang Lieb and Andre Franke and Jeanette Erdmann and Henrik Dommisch and Schaefer, {Arne S.}",
year = "2019",
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Munz, M, Richter, GM, Loos, BG, Jepsen, S, Divaris, K, Offenbacher, S, Teumer, A, Holtfreter, B, Kocher, T, Bruckmann, C, Jockel-Schneider, Y, Graetz, C, Ahmad, I, Staufenbiel, I, Van Der Velde, N, Uitterlinden, AG, De Groot, LCPGM, Wellmann, J, Berger, K, Krone, B, Hoffmann, P, Laudes, M, Lieb, W, Franke, A, Erdmann, J, Dommisch, H & Schaefer, AS 2019, 'Meta-analysis of genome-wide association studies of aggressive and chronic periodontitis identifies two novel risk loci', European Journal of Human Genetics, vol. 27, no. 1, pp. 102-113. https://doi.org/10.1038/s41431-018-0265-5

Meta-analysis of genome-wide association studies of aggressive and chronic periodontitis identifies two novel risk loci. / Munz, Matthias; Richter, Gesa M.; Loos, Bruno G.; Jepsen, Søren; Divaris, Kimon; Offenbacher, Steven; Teumer, Alexander; Holtfreter, Birte; Kocher, Thomas; Bruckmann, Corinna; Jockel-Schneider, Yvonne; Graetz, Christian; Ahmad, Ilyas; Staufenbiel, Ingmar; Van Der Velde, Nathalie; Uitterlinden, André G.; De Groot, Lisette C.P.G.M.; Wellmann, Jürgen; Berger, Klaus; Krone, Bastian; Hoffmann, Per; Laudes, Matthias; Lieb, Wolfgang; Franke, Andre; Erdmann, Jeanette; Dommisch, Henrik; Schaefer, Arne S.

In: European Journal of Human Genetics, Vol. 27, No. 1, 2019, p. 102-113.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Meta-analysis of genome-wide association studies of aggressive and chronic periodontitis identifies two novel risk loci

AU - Munz, Matthias

AU - Richter, Gesa M.

AU - Loos, Bruno G.

AU - Jepsen, Søren

AU - Divaris, Kimon

AU - Offenbacher, Steven

AU - Teumer, Alexander

AU - Holtfreter, Birte

AU - Kocher, Thomas

AU - Bruckmann, Corinna

AU - Jockel-Schneider, Yvonne

AU - Graetz, Christian

AU - Ahmad, Ilyas

AU - Staufenbiel, Ingmar

AU - Van Der Velde, Nathalie

AU - Uitterlinden, André G.

AU - De Groot, Lisette C.P.G.M.

AU - Wellmann, Jürgen

AU - Berger, Klaus

AU - Krone, Bastian

AU - Hoffmann, Per

AU - Laudes, Matthias

AU - Lieb, Wolfgang

AU - Franke, Andre

AU - Erdmann, Jeanette

AU - Dommisch, Henrik

AU - Schaefer, Arne S.

PY - 2019

Y1 - 2019

N2 - Periodontitis is one of the most common inflammatory diseases, with a prevalence of 11% worldwide for the severe forms and an estimated heritability of 50%. It is classified into the widespread moderate form chronic periodontitis (CP) and the rare early-onset and severe phenotype aggressive periodontitis (AgP). These different disease manifestations are thought to share risk alleles and predisposing environmental factors. To obtain novel insights into the shared genetic etiology and the underlying molecular mechanisms of both forms, we performed a two step-wise meta-analysis approach using genome-wide association studies of both phenotypes. Genotypes from imputed genome-wide association studies (GWAS) of AgP and CP comprising 5,095 cases and 9,908 controls of North-West European genetic background were included. Two loci were associated with periodontitis at a genome-wide significance level. They located within the pseudogene MTND1P5 on chromosome 8 (rs16870060-G, P = 3.69 × 10−9, OR = 1.36, 95% CI = [1.23–1.51]) and intronic of the long intergenic non-coding RNA LOC107984137 on chromosome 16, downstream of the gene SHISA9 (rs729876-T, P = 9.77 × 10−9, OR = 1.24, 95% CI = [1.15–1.34]). This study identified novel risk loci of periodontitis, adding to the genetic basis of AgP and CP.

AB - Periodontitis is one of the most common inflammatory diseases, with a prevalence of 11% worldwide for the severe forms and an estimated heritability of 50%. It is classified into the widespread moderate form chronic periodontitis (CP) and the rare early-onset and severe phenotype aggressive periodontitis (AgP). These different disease manifestations are thought to share risk alleles and predisposing environmental factors. To obtain novel insights into the shared genetic etiology and the underlying molecular mechanisms of both forms, we performed a two step-wise meta-analysis approach using genome-wide association studies of both phenotypes. Genotypes from imputed genome-wide association studies (GWAS) of AgP and CP comprising 5,095 cases and 9,908 controls of North-West European genetic background were included. Two loci were associated with periodontitis at a genome-wide significance level. They located within the pseudogene MTND1P5 on chromosome 8 (rs16870060-G, P = 3.69 × 10−9, OR = 1.36, 95% CI = [1.23–1.51]) and intronic of the long intergenic non-coding RNA LOC107984137 on chromosome 16, downstream of the gene SHISA9 (rs729876-T, P = 9.77 × 10−9, OR = 1.24, 95% CI = [1.15–1.34]). This study identified novel risk loci of periodontitis, adding to the genetic basis of AgP and CP.

U2 - 10.1038/s41431-018-0265-5

DO - 10.1038/s41431-018-0265-5

M3 - Article

VL - 27

SP - 102

EP - 113

JO - European Journal of Human Genetics

T2 - European Journal of Human Genetics

JF - European Journal of Human Genetics

SN - 1018-4813

IS - 1

ER -