Shared Genetic Contributions Between Oral and General Health Using GWAS in 506,667 Adults

Objectives: Numerous epidemiological correlations between measures of oral and general health are reported in the literature. All such correlations (with cardiovascular disease, obesity, asthma or behavioural disorders, etc) fail to correctly represent shared genetic overlap between oral and general health traits, mostly due to complex cross-correlated nature of multiple factors implicated in disease development. However, information on shared genetic underpinnings between diseases can be useful for understanding common biology or pathway effects between them. Our aim was to use large-scale genome-wide association studies (GWAS) meta-analysis for dental diseases and published GWAS meta-analyses for general health-related traits to estimate the shared portion of heritable genetic contributions to oral and general health measures
Methods: We applied linkage disequilibrium score regression using GWAS data to calculate all-SNP genetic correlations (r_g) for pairs of oral-general heath traits. We used GWAS for clinically assessed measures of caries and periodontal diseases (n=26,792 and 45,561 adults respectively), as well their joint meta-analysis with self-reported dental measures (n=487,898 and 506,667 respectively). For other health outcomes, we used 128 published GWAS for disease traits from broader groups of anthropometric, autoimmune, cancer, cardiometabolic, glycemic, behavioural, psychiatric and reproductive health traits
Results: We calculated a total of 256 r_g for studied traits. For caries, the all-SNP based heritability estimate was 0.098 (se=0.016) and among the strongest r_g values (P_FDR<0.05) were with smoking (r_g=0.51), attention deficit hyperactivity (r_g=0.39), waist-hip ratio (r_g=0.25), body mass index (r_g=0.21) and HDL-cholesterol (r_g=-0.18). For periodontal health, all-SNP based heritability estimate was 0.011 (se=0.009) and among strongest r_g values (P_FDR<0.05) were with smoking (r_g=0.64), lung cancer (r_g=0.56), insomnia (r_g=0.34), body fat (r_g=0.33), type 2 diabetes (rg=0.20) and coronary artery disease (r_g=0.16)
Conclusions: This large-scale study of genetic overlap for dental diseases mapped multiple genetic correlations with a wide range of disease traits, elucidating shared genetic determinants and shedding new light on potential common biology in complex relationships between oral and general health