Genome-wide association study of chronic periodontitis in a general German population

Aim To identify loci associated with chronic periodontitis through a genome‐wide association study (GWAS). Materials and Methods A GWAS was performed in 4032 individuals of two independent cross‐sectional studies of West Pomerania (SHIP n = 3365 and SHIP‐TREND n = 667) with different periodontal cas...

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Vydáno v:	Journal of clinical periodontology Ročník 40; číslo 11; s. 977 - 985
Hlavní autoři:	Teumer, Alexander, Holtfreter, Birte, Völker, Uwe, Petersmann, Astrid, Nauck, Matthias, Biffar, Reiner, Völzke, Henry, Kroemer, Heyo K., Meisel, Peter, Homuth, Georg, Kocher, Thomas
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Blackwell Publishing Ltd 01.11.2013
Témata:	Adenine Adult Age Factors Aged Aged, 80 and over attachment loss Chromosomes, Human, X - genetics Chronic Periodontitis - genetics Cohort Studies Cross-Sectional Studies Cytosine Dentistry Female Follow-Up Studies Genetic Variation - genetics genome-wide association studies Genome-Wide Association Study Genomics Genotype Germany Gum disease HapMap Project Humans INDEL Mutation - genetics Male Middle Aged Periodontal Attachment Loss - genetics Periodontal Pocket - genetics periodontitis Polymorphism, Single Nucleotide - genetics Population Surveillance Study of Health in Pomerania Thymine Young Adult Germany Study of Health in Pomerania genome-wide association studies attachment loss periodontitis
ISSN:	0303-6979, 1600-051X, 1600-051X
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Abstract	Aim To identify loci associated with chronic periodontitis through a genome‐wide association study (GWAS). Materials and Methods A GWAS was performed in 4032 individuals of two independent cross‐sectional studies of West Pomerania (SHIP n = 3365 and SHIP‐TREND n = 667) with different periodontal case definitions. Samples were genotyped with the Affymetrix Genome‐Wide Human SNP Array 6.0 or the Illumina Human Omni 2.5 array. Imputation of the HapMap as well as the 1000 Genome‐based autosomal and X‐chromosomal genotypes and short insertions and deletions (INDELs) was performed in both cohorts. Finally, more than 17 million SNPs and short INDELs were analysed. Results No genome‐wide significant associations were found for any periodontitis case definition, regardless of whether individuals aged >60 years where excluded or not. Despite no single SNP association reached genome‐wide significance, the proportion of variance explained by additive effects of all common SNPs was around 23% for mean proximal attachment loss. Excluding subjects aged >60 years increased the explained variance to 34%. Conclusions No single SNPs were found to be genome‐wide significantly associated with chronic periodontitis in this study.
AbstractList	Aim To identify loci associated with chronic periodontitis through a genome‐wide association study (GWAS). Materials and Methods A GWAS was performed in 4032 individuals of two independent cross‐sectional studies of West Pomerania (SHIP n = 3365 and SHIP‐TREND n = 667) with different periodontal case definitions. Samples were genotyped with the Affymetrix Genome‐Wide Human SNP Array 6.0 or the Illumina Human Omni 2.5 array. Imputation of the HapMap as well as the 1000 Genome‐based autosomal and X‐chromosomal genotypes and short insertions and deletions (INDELs) was performed in both cohorts. Finally, more than 17 million SNPs and short INDELs were analysed. Results No genome‐wide significant associations were found for any periodontitis case definition, regardless of whether individuals aged >60 years where excluded or not. Despite no single SNP association reached genome‐wide significance, the proportion of variance explained by additive effects of all common SNPs was around 23% for mean proximal attachment loss. Excluding subjects aged >60 years increased the explained variance to 34%. Conclusions No single SNPs were found to be genome‐wide significantly associated with chronic periodontitis in this study. Aim To identify loci associated with chronic periodontitis through a genome-wide association study (GWAS). Materials and Methods A GWAS was performed in 4032 individuals of two independent cross-sectional studies of West Pomerania (SHIPn = 3365 and SHIP-TRENDn = 667) with different periodontal case definitions. Samples were genotyped with the Affymetrix Genome-Wide Human SNP Array 6.0 or the Illumina Human Omni 2.5 array. Imputation of the HapMap as well as the 1000 Genome-based autosomal and X-chromosomal genotypes and short insertions and deletions (INDELs) was performed in both cohorts. Finally, more than 17 million SNPs and short INDELs were analysed. Results No genome-wide significant associations were found for any periodontitis case definition, regardless of whether individuals aged >60 years where excluded or not. Despite no single SNP association reached genome-wide significance, the proportion of variance explained by additive effects of all common SNPs was around 23% for mean proximal attachment loss. Excluding subjects aged >60 years increased the explained variance to 34%. Conclusions No single SNPs were found to be genome-wide significantly associated with chronic periodontitis in this study. [PUBLICATION ABSTRACT] To identify loci associated with chronic periodontitis through a genome-wide association study (GWAS).AIMTo identify loci associated with chronic periodontitis through a genome-wide association study (GWAS).A GWAS was performed in 4032 individuals of two independent cross-sectional studies of West Pomerania (SHIP n = 3365 and SHIP-TREND n = 667) with different periodontal case definitions. Samples were genotyped with the Affymetrix Genome-Wide Human SNP Array 6.0 or the Illumina Human Omni 2.5 array. Imputation of the HapMap as well as the 1000 Genome-based autosomal and X-chromosomal genotypes and short insertions and deletions (INDELs) was performed in both cohorts. Finally, more than 17 million SNPs and short INDELs were analysed.MATERIALS AND METHODSA GWAS was performed in 4032 individuals of two independent cross-sectional studies of West Pomerania (SHIP n = 3365 and SHIP-TREND n = 667) with different periodontal case definitions. Samples were genotyped with the Affymetrix Genome-Wide Human SNP Array 6.0 or the Illumina Human Omni 2.5 array. Imputation of the HapMap as well as the 1000 Genome-based autosomal and X-chromosomal genotypes and short insertions and deletions (INDELs) was performed in both cohorts. Finally, more than 17 million SNPs and short INDELs were analysed.No genome-wide significant associations were found for any periodontitis case definition, regardless of whether individuals aged >60 years where excluded or not. Despite no single SNP association reached genome-wide significance, the proportion of variance explained by additive effects of all common SNPs was around 23% for mean proximal attachment loss. Excluding subjects aged >60 years increased the explained variance to 34%.RESULTSNo genome-wide significant associations were found for any periodontitis case definition, regardless of whether individuals aged >60 years where excluded or not. Despite no single SNP association reached genome-wide significance, the proportion of variance explained by additive effects of all common SNPs was around 23% for mean proximal attachment loss. Excluding subjects aged >60 years increased the explained variance to 34%.No single SNPs were found to be genome-wide significantly associated with chronic periodontitis in this study.CONCLUSIONSNo single SNPs were found to be genome-wide significantly associated with chronic periodontitis in this study. To identify loci associated with chronic periodontitis through a genome-wide association study (GWAS). A GWAS was performed in 4032 individuals of two independent cross-sectional studies of West Pomerania (SHIP n = 3365 and SHIP-TREND n = 667) with different periodontal case definitions. Samples were genotyped with the Affymetrix Genome-Wide Human SNP Array 6.0 or the Illumina Human Omni 2.5 array. Imputation of the HapMap as well as the 1000 Genome-based autosomal and X-chromosomal genotypes and short insertions and deletions (INDELs) was performed in both cohorts. Finally, more than 17 million SNPs and short INDELs were analysed. No genome-wide significant associations were found for any periodontitis case definition, regardless of whether individuals aged >60 years where excluded or not. Despite no single SNP association reached genome-wide significance, the proportion of variance explained by additive effects of all common SNPs was around 23% for mean proximal attachment loss. Excluding subjects aged >60 years increased the explained variance to 34%. No single SNPs were found to be genome-wide significantly associated with chronic periodontitis in this study.
Author	Kroemer, Heyo K. Teumer, Alexander Meisel, Peter Völzke, Henry Kocher, Thomas Biffar, Reiner Petersmann, Astrid Nauck, Matthias Homuth, Georg Völker, Uwe Holtfreter, Birte
Author_xml	– sequence: 1 givenname: Alexander surname: Teumer fullname: Teumer, Alexander organization: Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany – sequence: 2 givenname: Birte surname: Holtfreter fullname: Holtfreter, Birte organization: Unit of Periodontology, Department of Restorative Dentistry, Periodontology and Endodontology, University Medicine Greifswald, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany – sequence: 3 givenname: Uwe surname: Völker fullname: Völker, Uwe organization: Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany – sequence: 4 givenname: Astrid surname: Petersmann fullname: Petersmann, Astrid organization: Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany – sequence: 5 givenname: Matthias surname: Nauck fullname: Nauck, Matthias organization: Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany – sequence: 6 givenname: Reiner surname: Biffar fullname: Biffar, Reiner organization: Department of Prosthetic Dentistry, Gerostomatology and Dental Materials, University Medicine Greifswald, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany – sequence: 7 givenname: Henry surname: Völzke fullname: Völzke, Henry organization: Institute for Community Medicine, University Medicine Greifswald, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany – sequence: 8 givenname: Heyo K. surname: Kroemer fullname: Kroemer, Heyo K. organization: Department of Pharmacology, Center of Drug Absorption and Transport (CDAT), University Medicine Greifswald, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany – sequence: 9 givenname: Peter surname: Meisel fullname: Meisel, Peter organization: Unit of Periodontology, Department of Restorative Dentistry, Periodontology and Endodontology, University Medicine Greifswald, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany – sequence: 10 givenname: Georg surname: Homuth fullname: Homuth, Georg organization: Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany – sequence: 11 givenname: Thomas surname: Kocher fullname: Kocher, Thomas email: Address:, kocher@uni-greifswald.de organization: Unit of Periodontology, Department of Restorative Dentistry, Periodontology and Endodontology, University Medicine Greifswald, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/24024966$$D View this record in MEDLINE/PubMed
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Keywords	Study of Health in Pomerania genome-wide association studies attachment loss periodontitis
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Notes	Ministry of Cultural Affairs Siemens Healthcare istex:86D83FDE9BABF430CA4475903E71C429C2BB21A8 ArticleID:JCPE12154 GABA Social Ministry of the Federal State of Mecklenburg-West Pomerania Figure S1. GWAS results quantile-quantile plots of all analyzed traits. (a) mean PAL (all individuals); (b) mean PAL (age ≤60 years); (c) PAL4Q3 (all individuals); (d) PAL4Q3 (age ≤60 years); (e) CDC/AAP (all individuals); (f) CDC/AAP (age ≤60 years); (g) DPAL (all individuals); (h) DPAL (age ≤60 years); (i) mean PAL (1000G); (j) CDC/AAP (1000G). Figure S2. GWAS results quantile-quantile plots of SHIP used for meta-analysis. (a) mean PAL (all individuals); (b) mean PAL (age ≤60 years); (c) PAL4Q3 (all individuals); (d) PAL4Q3 (age ≤60 years); (e) CDC/AAP (all individuals); (f) CDC/AAP (age ≤60 years); (g) mean PAL (1000G); (h) CDC/AAP (1000G).Figure S3. GWAS results quantile-quantile plots of SHIP-TREND used for meta-analysis. (a) mean PAL (all individuals); (b) mean PAL (age ≤60 years); (c) PAL4Q3 (all individuals); (d) PAL4Q3 (age ≤60 years); (e) CDC/AAP (all individuals); (f) CDC/AAP (age ≤60 years); (g) mean PAL (1000G); (h) CDC/AAP (1000G). Figure S4. Comparison of the effect sizes of the top SNPs reported in Divaris et al. (ARIC) with the CDC/AAP (all individuals) results. The effects directions are set to have higher odds of chronic periodontitis in the ARIC sample. The SNP identifier and the name of the closest gene are shown. Table S1. Information on genotyping and imputation. Table S2. GWAS results on mean proximal attachment loss related phenotypes with GC corrected p-value < 1E-5 after quality control filters. All individuals were included (meta-analysis of SHIP and SHIP-TREND cohorts, N = 4032). Table S3. GWAS results on periodontitis with GC corrected p-value < 1E-5 after quality control filters. Subjects within the first versus the third tertile of proportion of proximal sites with AL ≥4 mm were opposed. All individuals were included (meta-analysis of SHIP and SHIP-TREND cohorts, N = 2969). Table S4. GWAS results on the CDC/AAP case definition for periodontitis (Page & Eke ) with GC corrected p-value < 1E-5 after quality control filters. All individuals were included (meta-analysis of SHIP and SHIP-TREND cohorts, N = 3915). Table S5. GWAS results on 5-year change in mean proximal attachment loss related phenotypes with GC corrected p-value < 1E-5 after quality control filters. All individuals were included (SHIP cohort, N=2501). Table S6 GWAS results on mean proximal attachment loss with GC corrected p-value < 1E-5 after quality control filters. Individuals aged >60 years were excluded (meta-analysis of SHIP and SHIP-TREND cohorts, N=3189). Table S7. GWAS results on periodontitis with GC corrected p-value < 1E-5 after quality control filters. Subjects within the first versus the third tertile of proportion of proximal sites with AL ≥4 mm were opposed. Individuals aged >60 years were excluded (meta-analysis of SHIP and SHIP-TREND cohorts, N = 2412). Table S8. GWAS results on the CDC/AAP case definition for periodontitis (Page & Eke ) with GC corrected p-value < 1E-5 after quality control filters. Individuals aged >60 years were excluded (meta-analysis of SHIP and SHIP-TREND cohorts, N = 3151). Table S9. GWAS results on 5-year change in mean proximal attachment loss related phenotypes with GC corrected p-value < 1E-5 after quality control filters. Individuals aged >60 years were excluded (SHIP cohort, N = 2098). Table S10. GWAS results on proximal attachment loss related phenotypes with GC corrected p-value < 1E-5 after quality control filters using the 1000 Genomes imputation. Individuals aged >60 years were excluded (meta-analysis of SHIP and SHIP-TREND cohorts, N = 3189). Table S11. GWAS results on the CDC/AAP case definition for periodontitis (Page & Eke ) with GC corrected p-value < 1E-5 after quality control filters using the 1000 Genomes imputation. Individuals aged >60 years excluded (meta-analysis of SHIP and SHIP-TREND cohorts, N = 3151). ark:/67375/WNG-ZNGPC76D-V Federal Ministry of Education and Research - No. 01ZZ9603; No. 01ZZ0103; No. 01ZZ0403; No. 03IS2061A; No. 03ZIK012 http://www.community-medicine.de There are no conflicts of interest associated with this study. SHIP is part of the Community Medicine Research net (CMR Conflict of interest and source of funding statement of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg‐West Pomerania, and the network “Greifswald Approach to Individualized Medicine (GANI_MED)” funded by the Federal Ministry of Education and Research (grant 03IS2061A). This study was granted by BMBF‐01‐ZZ‐9603/0 and BH was supported by GABA, Switzerland. Generation of genome‐wide SNP data has been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany and the Federal State of Mecklenburg, West Pomerania. The University of Greifswald is a member of the “Center of Knowledge Interchange” programme of the Siemens AG and the Caché Campus programme of the InterSystems GmbH. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
PMID	24024966
PQID	1439165625
PQPubID	105484
PageCount	9
ParticipantIDs	proquest_miscellaneous_1447108184 proquest_journals_1439165625 pubmed_primary_24024966 crossref_citationtrail_10_1111_jcpe_12154 crossref_primary_10_1111_jcpe_12154 wiley_primary_10_1111_jcpe_12154_JCPE12154 istex_primary_ark_67375_WNG_ZNGPC76D_V
PublicationCentury	2000
PublicationDate	November 2013
PublicationDateYYYYMMDD	2013-11-01
PublicationDate_xml	– month: 11 year: 2013 text: November 2013
PublicationDecade	2010
PublicationPlace	United States
PublicationPlace_xml	– name: United States – name: Malden
PublicationTitle	Journal of clinical periodontology
PublicationTitleAlternate	J Clin Periodontol
PublicationYear	2013
Publisher	Blackwell Publishing Ltd
Publisher_xml	– name: Blackwell Publishing Ltd
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Snippet	Aim To identify loci associated with chronic periodontitis through a genome‐wide association study (GWAS). Materials and Methods A GWAS was performed in 4032... To identify loci associated with chronic periodontitis through a genome-wide association study (GWAS). A GWAS was performed in 4032 individuals of two... Aim To identify loci associated with chronic periodontitis through a genome-wide association study (GWAS). Materials and Methods A GWAS was performed in 4032... To identify loci associated with chronic periodontitis through a genome-wide association study (GWAS).AIMTo identify loci associated with chronic periodontitis...
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SubjectTerms	Adenine Adult Age Factors Aged Aged, 80 and over attachment loss Chromosomes, Human, X - genetics Chronic Periodontitis - genetics Cohort Studies Cross-Sectional Studies Cytosine Dentistry Female Follow-Up Studies Genetic Variation - genetics genome-wide association studies Genome-Wide Association Study Genomics Genotype Germany Gum disease HapMap Project Humans INDEL Mutation - genetics Male Middle Aged Periodontal Attachment Loss - genetics Periodontal Pocket - genetics periodontitis Polymorphism, Single Nucleotide - genetics Population Surveillance Study of Health in Pomerania Thymine Young Adult
Title	Genome-wide association study of chronic periodontitis in a general German population
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