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ABSTRACT
BackgroundElectronic health records provides unprecedented opportunity for their re-use in genetic epidemiological research. However, electronic health records data from clinical settings, such as dental practices may be inaccurate or of insufficient granularity to be of use in research. In this study, we wish to determine the utility of National Health Service (NHS) electronic dental treatment records in genetic epidemiological research.
ObjectiveTo estimate the heritability of periodontal disease using NHS electronic dental treatment records linked to health and non-health data within the Generation Scotland: Scottish Family Health Study (GS:SFHS).
ApproachWe linked 852,355 NHS Scotland electronic dental treatment records from April 2000 to July 2015 to 20,626 participants within the GS:SFHS with pedigree, genomic, sociodemographic and clinical data. We then conducted a proof-of-principle genetic epidemiological analysis using periodontal (gum) disease treatment records. The data set analysed, consisted of 160,508 dental treatment records from 13,717 study participants; 3,387 of which were periodontal treatment records (from 2,192 study participants). We adjusted for the effects of previous treatment record, interval since last treatment, age, sex, treatment year, and treatment month, Scottish index of multiple deprivation, alcohol consumption, diabetes diagnosis, and smoking status in a linear model in the statistical software ASReml. We then calculated the mean risk of periodontal disease for each study participant based on residuals extracted from the aforementioned model. Genome-complex trait analysis (GCTA; with correction for population stratification) was used to estimate the pedigree and genomic based heritability of periodontal disease.
ResultsWe estimate the familial heritability of periodontal (gum) disease at 10.42% (95% confidence interval 5.97-14.88%). The genomic component did not contribute significantly to the heritability estimate.
Conclusionwe have demonstrated the usefulness of electronic dental treatment records in population based genetic epidemiological research .This study has also, to the best of our knowledge provided the first population based estimates of the genetic parameters for periodontal disease; confirming its familial nature. This invaluable and unique data resource will allow the acceleration of oral health research in Scotland and the exploration of research questions that could not be considered previously.

IntroductionHeritability (proportion of trait variation attributable to genetic factors) is not a fixed property. It can vary across different social settings and environments. Exploration of gene-environment interaction has been limited by lack of large sample sizes. Biobanks linked to electronic health records pose a solution to this sample size problem.
Objectives and ApproachSocial inequalities in periodontal health have been well documented in the dental scientific literature. However, gene-socioeconomic status interaction has yet to be examined. We identified 2,192 cases and 11,525 controls from linked electronic periodontal treatment records within the Generation Scotland: Scottish Family Health Study (GS: SFHS) (www.generationscotland.org). The measure of socioeconomic status used was the Scottish Index of Multiple Deprivation. The objective of this study was to investigate the gene-socioeconomic status interaction within this data. A reaction norm model was used to evaluate the presence of a gene-socioeconomic status interaction in the statistical software ASReml.
ResultsWe estimated the heritability of periodontal disease at 10.42% (95% confidence interval 5.97-14.88%). Socioeconomic status modified the heritability of periodontal disease. The heritability of was 13.37%, 0.14% and 11.70% in areas of high, moderate and low deprivation respectively; indicating the occurrence of a gene-socioeconomic status interaction with periodontal disease. These results indicate that socioeconomic status explains a large portion of genetic variation in periodontal disease risk. This information suggests that effective intervention and prevention programs for periodontal disease should involve socioeconomic aspects in their planning, implementations and evaluation. For instance, interventions targeted to reduce smoking in more deprived subjects with a genetic predisposition to periodontal disease could enhance the effect of health promotion strategies in reducing risk.
Conclusion/ImplicationsThis study presents contemporary evidence in a large population based cohort that gene-socioeconomic interaction leads to the progression of periodontal disease. This information may lead to the development of better preventative strategies for clinical dentistry.

Strains of many infectious diseases differ in parameters that influence epidemic spread, for example virulence, transmissibility, detectability and host specificity. Knowledge of inter-strain variation can be exploited to improve management and decrease disease incidence. Bovine tuberculosis (bTB) is increasingly prevalent among farmed cattle in the UK, exerting a heavy economic burden on the farming industry and government. We aimed to determine whether strains of Mycobacterium bovis (the causative agent of bTB) identified and classified using genetic markers (spoligotyping and multi-locus VNTR analysis) varied in response to the tuberculin skin test; this being the primary method of bTB detection used in the UK. Inter-strain variation in detectability of M. bovis could have important implications for disease control. The skin test is based on a differential delayed type hypersensitivity (DTH) response to intradermal injections of purified protein derivative (PPD) from M. bovis (PPD-B) and Mycobacterium avium (PPD-A). We searched for an association between skin test response (PPD-B skin rise minus PPD-A skin rise) and M. bovis genotype at the disclosing test in culture-confirmed cases using a field dataset consisting of 21,000 isolates belonging to 63 genotypes of M. bovis from cattle in Northern Ireland. We found no substantial variation among genotypes (estimated responses clustered tightly around the mean) controlling for animal sex, breed and test effects. We also estimated the ratio of skin test detected to undetected cases (i.e. cases only detected at abattoir). The skin test detection ratio varied among abattoirs with some detecting a greater proportion of cases than others but this variation was unrelated to the community composition of genotypes within each abattoir catchment. These two lines of evidence indicate that M. bovis genotypes in Northern Ireland have similar detectability using the skin test.

Acknowledgements: This work was supported by Alzheimer's Research UK Major Project Grant [ARUK–PG2017B–10]. Generation Scotland received core funding from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006]. We are grateful to all the families who took part, the general practitioners and the Scottish School of Primary Care for their help in recruiting them, and the whole Generation Scotland team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, healthcare assistants, and nurses. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award "STratifying Resilience and Depression Longitudinally" (STRADL) [104036/Z/14/Z]. DNA methylation data collection was funded by the Wellcome Trust Strategic Award [10436/Z/14/Z]. The research was conducted in The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE), part of the cross–council Lifelong Health and Wellbeing Initiative [MR/K026992/1]; funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged. CCACE supports Ian Deary, with some additional support from Dementias Platform UK [MR/L015382/1]. HCW is supported by a JMAS SIM fellowship from the Royal College of Physicians of Edinburgh. AMM and HCW have received support from the Sackler Institute ; Peer reviewed ; Publisher PDF