E. Stankevic, Y. Huang, I. C. Pereda, S. He, E. Joersboe, M. Thodberg, F. Geller, L. Angquist, L. M. Pikkupeura, C. Mikkelsen, N. Nygaard, M. Markvart, S. E. Stinson, L. Niu, A. R. Poggi, L. A. Holm, C. E. Fonvig, J.-C. Holm, J. Ghouse, K. Banasik, M. T. Bruun, S. G. Saekmose, B. Aagaard, E. Soerensen, H. Ullum, K. Stefansson, H. Stefansson, D. F. Gudbjartsson, U. Thorsteinsdottir, P. Sulem, I. Jonsdottir, A. Helgasdottir, DBDS Genomic Consortium, N. Grarup, M. Mann, D. Belstroem, A. Olsen, H. Bundgaard, S. Brunak, C. Erikstrup, B. Feenstra, Ostrowski
Emerging evidence indicates that oral and systemic health are interconnected, yet the basis of this relationship remains incompletely understood. In a genome-wide association study of objectively measured dental caries in permanent dentition among Danish children and adolescents (DCCA) (N = 151,521), we identified 14 independent loci. Genes at DCCA-associated loci were enriched for expression in immune, secretory and epithelial cell populations. We found genetic correlations and evidence for shared causal variants with several cardiometabolic traits. Leveraging data from UK Biobank (Nmax = 501,936) and independent pediatric cohorts (Nmax = 3,412), we showed that genetic liability to DCCA associated with dentures, risk of coronary artery disease and type 2 diabetes in adults, and with HbA1C, lipid, liver enzyme levels, and plasma proteins implicated in oral, metabolic and hepatic biology in both populations. Our results provide new insights into the genetic architecture underlying the relationship between DCCA and cardiometabolic disease.