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      Biomarkers for Lifetime Caries-Free Status

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          Abstract

          The purpose of this study was to address the hypothesis that extreme outcomes of dental caries, such as edentulism or prematurely losing permanent teeth are associated with genetic variation in enamel-formation genes. After scanning 6206 individuals, samples of 330 were selected for this study. Tested phenotypes included patients who were edentulous by age 30, patients with missing first molars by age 30, patients with missing second molars by age 30, and caries-free patients. Fourteen single nucleotide polymorphisms were genotyped by TaqMan chemistry. The analyses of each phenotype were performed using the software PLINK with an alpha of 0.05. Nominal associations were found between rs12640848 in enamelin ( p = 0.05), rs1784418 in matrix metallopeptidase 20 ( p = 0.02), and rs5997096 in the tuftelin interacting protein 11 and being caries-free at the age of 60. When combining patients that were missing both first mandibular molars and missing both second mandibular molars, no associations were found. Matrix metallopeptidase 20, and tuftelin interacting protein 11 also showed trends for association with being caries-free. Genetic variation in TFIP11, MMP20, and ENAM may have a protective effect increasing the chances of individuals preserving their teeth caries-free over a lifetime.

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          PLINK: a tool set for whole-genome association and population-based linkage analyses.

          Shaun Purcell, Benjamin M. Neale, Kathe Todd-Brown … (2007)
          Whole-genome association studies (WGAS) bring new computational, as well as analytic, challenges to researchers. Many existing genetic-analysis tools are not designed to handle such large data sets in a convenient manner and do not necessarily exploit the new opportunities that whole-genome data bring. To address these issues, we developed PLINK, an open-source C/C++ WGAS tool set. With PLINK, large data sets comprising hundreds of thousands of markers genotyped for thousands of individuals can be rapidly manipulated and analyzed in their entirety. As well as providing tools to make the basic analytic steps computationally efficient, PLINK also supports some novel approaches to whole-genome data that take advantage of whole-genome coverage. We introduce PLINK and describe the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation. In particular, we focus on the estimation and use of identity-by-state and identity-by-descent information in the context of population-based whole-genome studies. This information can be used to detect and correct for population stratification and to identify extended chromosomal segments that are shared identical by descent between very distantly related individuals. Analysis of the patterns of segmental sharing has the potential to map disease loci that contain multiple rare variants in a population-based linkage analysis.
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            The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.

            Erik von Elm, Douglas G. Altman, Matthias Egger … (2008)
            Much of biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study's generalizability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September 2004, with methodologists, researchers, and journal editors to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE Statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles. Eighteen items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies. A detailed Explanation and Elaboration document is published separately and is freely available on the web sites of PLoS Medicine, Annals of Internal Medicine, and Epidemiology. We hope that the STROBE Statement will contribute to improving the quality of reporting of observational studies.
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              Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data

              Dmitry Shungin, Simon Haworth, Kimon Divaris … (2019)
              Dental caries and periodontitis account for a vast burden of morbidity and healthcare spending, yet their genetic basis remains largely uncharacterized. Here, we identify self-reported dental disease proxies which have similar underlying genetic contributions to clinical disease measures and then combine these in a genome-wide association study meta-analysis, identifying 47 novel and conditionally-independent risk loci for dental caries. We show that the heritability of dental caries is enriched for conserved genomic regions and partially overlapping with a range of complex traits including smoking, education, personality traits and metabolic measures. Using cardio-metabolic traits as an example in Mendelian randomization analysis, we estimate causal relationships and provide evidence suggesting that the processes contributing to dental caries may have undesirable downstream effects on health.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Pers Med
                Journal ID (iso-abbrev): J Pers Med
                Journal ID (publisher-id): jpm
                Title: Journal of Personalized Medicine
                Publisher: MDPI
                ISSN (Electronic): 2075-4426
                Publication date (Electronic): 30 December 2020
                Publication date Collection: January 2021
                Volume: 11
                Issue: 1
                Electronic Location Identifier: 23
                Affiliations
                School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA; amk211@ 123456pitt.edu (A.M.K.); mbl29@ 123456pitt.edu (M.B.); ams208@ 123456pitt.edu (A.M.)
                Author notes
                [* ]Correspondence: arv11@ 123456pitt.edu ; Tel.: +1-412-383-8972
                Author information
                https://orcid.org/0000-0001-9397-3167
                https://orcid.org/0000-0003-3392-6881
                Article
                Publisher ID: jpm-11-00023
                DOI: 10.3390/jpm11010023
                PMC ID: 7824168
                PubMed ID: 33396693
                SO-VID: 9c0c815d-bd3d-4341-add6-65fa92b0146a
                Copyright © © 2020 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 26 November 2020
                Date accepted : 28 December 2020
                Categories
                Subject: Article

                Keywords: dental caries,edentulism,genomics
                Data availability:
                Keywords: dental caries, edentulism, genomics

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