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Pilot GWAS of caries in African-Americans shows genetic heterogeneity.

ABSTRACT: BACKGROUND:Dental 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. METHODS:We 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. RESULTS:No 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

SUBMITTER: Orlova E

PROVIDER: S-EPMC6751797 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Pilot GWAS of caries in African-Americans shows genetic heterogeneity.

Orlova E E Carlson J C JC Lee M K MK Feingold E E McNeil D W DW Crout R J RJ Weyant R J RJ Marazita M L ML Shaffer J R JR

BMC oral health 20190918 1

<h4>Background</h4>Dental 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.<h4>Methods</h4>We performed exploratory GWAS of dental caries in 109 African American adults (age > ...[more]

PMID: 31533690

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Project description:BackgroundEarly childhood caries (ECC) is a rapidly progressing form of dental infection and a significant public health problem, especially among socially and economically disadvantaged populations. This study aimed to assess the risk factors for ECC among a cohort of Sub-Saharan African children and to determine the role of genetics in the etiology of ECC.MethodsA sample of 691 children (338 with ECC, 353 without ECC, age < 6 years) was recruited from schools in Lagos, Nigeria. Socio-demographic, dental services utilization and infant dietary data were obtained with interviewer-administered questionnaire. Oral examination was conducted using the WHO oral health diagnostic criteria. Saliva samples were collected from the children for genetic analysis. Single nucleotide polymorphisms were selected from previous study for genotyping. Genetic association analyses to investigate the role of genetics in the etiology of ECC was done. Bivariate comparisons and Multivariate logistic regression analyses were conducted to assess associations between ECC and predictor variables, p < 0.05.ResultsOf the 338 children with ECC, 64 (18.9%) had Severe-Early Childhood Caries (S-ECC). Children aged 48-59 months comprised the highest proportion of subjects with ECC (165; 48.8%) and S-ECC (24; 37.5%) while female subjects had higher dt (3.13 ± 2.56) and dmft values 3.27 ± 2.64. ECC was significantly more prevalent among children who were breastfed at night ≥ 12 months (OR 3.30; CI 0.39, 4.75), those with no previous dental visit (OR 1.71; CI 0.24, 2.77), those who used sweetened pacifiers (OR 1.85; CI 0.91, 3.79) and those who daily consumed sugar-sweetened drinks/snacks (OR 1.35; CI 0.09, 18.51). A suggestive increased risk for ECC (OR 1.26, p = 0. 0.0397) was observed for the genetic variant rs11239282 on chromosome 10. We also observed a suggestive reduced risk for ECC (OR 0.80, p = 0.03) for the rs131777 on chromosome 22. None of the genetic variants were significant after correction for multiple testing (Bonferroni p value p = 0.004).ConclusionsProlonged night-time breastfeeding, poor utilization of dental services and daily consumption of sugar were risk factors for ECC. Larger sample size is needed to confirm the results of the genetic analysis and to conduct genome wide studies in order to discover new risk loci for ECC.

Dataset Information

Pilot GWAS of caries in African-Americans shows genetic heterogeneity.

Publications

Pilot GWAS of caries in African-Americans shows genetic heterogeneity.

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