IADR Abstract Archives
Identifying Genes Underlying Lifetime Caries Risk in an Appalachian Sample
Objectives: Dental caries is a substantial public health risk for individuals of all ages and influenced by genetic and environmental factors. Here, we conducted genome-wide association analysis of caries experience combining primary and permanent dentitions, in order to investigate common genetic risks across both dentitions on subjects selected from an ongoing study of oral health and disease in the Appalachian region. We expect to identify genes affecting caries susceptibility over the subjects’ lifetime.
Methods: The phenotype was derived derived by adjusting the total of d2ft and D2MFT (decayed without precavitated lesions, missing and filled teeth) for age effects using LOESS polynomial regression. We analyzed 2,522 individuals with at least 20 teeth and approximately 5.7 million imputed and genotyped dimorphic variants. P-value thresholds for genomewide significant and suggestive association were set to 5e-08 and 1e-05 respectively.
Results: A significant association was observed at chr2q12.1 and suggestive associations at chr1q44, chr5q13.1, chr12p12.2 and chr16p12.3 harboring genes (FHL2, NLRP3, MAST4, ERI2 etc.) linked to obesity, type 2 diabetes, and auto-immune disorders such as AIDS, rheumatoid arthritis and inflammatory bowel disease. A near-suggestive association was observed near the FAM118A gene previously found in a meta-analysis of caries (PMID 31235808).
Conclusions: We conclude that genes belonging to inflammation response pathways may mediate the lifetime risk of dental caries severity. Further, the use of a new caries phenotype may explain why we did not replicate previously reported loci.
Methods: The phenotype was derived derived by adjusting the total of d2ft and D2MFT (decayed without precavitated lesions, missing and filled teeth) for age effects using LOESS polynomial regression. We analyzed 2,522 individuals with at least 20 teeth and approximately 5.7 million imputed and genotyped dimorphic variants. P-value thresholds for genomewide significant and suggestive association were set to 5e-08 and 1e-05 respectively.
Results: A significant association was observed at chr2q12.1 and suggestive associations at chr1q44, chr5q13.1, chr12p12.2 and chr16p12.3 harboring genes (FHL2, NLRP3, MAST4, ERI2 etc.) linked to obesity, type 2 diabetes, and auto-immune disorders such as AIDS, rheumatoid arthritis and inflammatory bowel disease. A near-suggestive association was observed near the FAM118A gene previously found in a meta-analysis of caries (PMID 31235808).
Conclusions: We conclude that genes belonging to inflammation response pathways may mediate the lifetime risk of dental caries severity. Further, the use of a new caries phenotype may explain why we did not replicate previously reported loci.
