Abstract
BackgroundDental caries is the most common chronic disease in the US and disproportionately affects racial/ethnic minorities. Caries is heritable, and though genetic heterogeneity exists between ancestries for a substantial portion of loci associated with complex disease, a genome-wide association study (GWAS) of caries specifically in African Americans has not been performed previously.MethodsWe performed exploratory GWAS of dental caries in 109 African American adults (age > 18) and 96 children (age 3–12) from the Center for Oral Health Research in Appalachia (COHRA1 cohort). Caries phenotypes (DMFS, DMFT, dft, and dfs indices) assessed by dental exams were tested for association with 5 million genotyped or imputed single nucleotide polymorphisms (SNPs), separately in the two age groups. The GWAS was performed using linear regression with adjustment for age, sex, and two principal components of ancestry. A maximum of 1 million adaptive permutations were run to determine empirical significance.ResultsNo loci met the threshold for genome-wide significance, though some of the strongest signals were near genes previously implicated in caries such as antimicrobial peptide DEFB1 (rs2515501; p = 4.54 × 10− 6) and TUFT1 (rs11805632; p = 5.15 × 10− 6). Effect estimates of lead SNPs at suggestive loci were compared between African Americans and Caucasians (adults N = 918; children N = 983). Significant (p < 5 × 10− 8) genetic heterogeneity for caries risk was found between racial groups for 50% of the suggestive loci in children, and 12–18% of the suggestive loci in adults.ConclusionsThe genetic heterogeneity results suggest that there may be differences in the contributions of genetic variants to caries across racial groups, and highlight the critical need for the inclusion of minorities in subsequent and larger genetic studies of caries in order to meet the goals of precision medicine and to reduce oral health disparities.
Highlights
Dental caries is the most common chronic disease in the US and disproportionately affects racial/ ethnic minorities
Results annotation and comparison with Caucasian caries genome-wide association study (GWAS) Genes within 500 kb of the top associated Single nucleotide polymorphism (SNP) in each locus were queried for corroborating biological connections to dental caries in public databases, including OMIM, PubMed, and ClinVar
The effect sizes for the lead SNPs at suggestive (p-value ≤5 × 10− 6) loci observed in African Americans were compared with the effect sizes of the same SNPs in Caucasians, if present
Summary
Dental caries is the most common chronic disease in the US and disproportionately affects racial/ ethnic minorities. Dental caries is a complex disease influenced by genetic and environmental factors, including diet, oral hygiene, oral bacteria such as Streptococcus mutans, tooth morphology and placement, the composition and flow rate of saliva, fluoride exposure, and access to oral health care [1,2,3,4]. According to the National Health and Nutrition Examination Survey (NHANES), caries affects the majority of children (i.e., 23% by age 5 years, 56% by age 8, 67% by age 19), and adults (91%) and is the most common chronic disease in the United States [9,10,11]. Caries has declined in the United States since the mid-twentieth century, the caries rate in young children has increased in recent years, and disparities persist between racial/ethnic, demographic, and socioeconomic
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