Journal article
Association of Early Childhood Caries with Bitter Taste Receptors: A Meta-Analysis of Genome-Wide Association Studies and Transcriptome-Wide Association Study
Genes, Vol.14(1), p.59
01/01/2023
DOI: 10.3390/genes14010059
PMCID: PMC9858612
PMID: 36672800
Abstract
Although genetics affects early childhood caries (ECC) risk, few studies have focused on finding its specific genetic determinants. Here, we performed genome-wide association studies (GWAS) in five cohorts of children (aged up to 5 years, total N = 2974, cohorts: Center for Oral Health Research in Appalachia cohorts one and two [COHRA1, COHRA2], Iowa Fluoride Study, Iowa Head Start, Avon Longitudinal Study of Parents and Children [ALSPAC]) aiming to identify genes with potential roles in ECC biology. We meta-analyzed the GWASs testing similar to 3.9 million genetic variants and found suggestive evidence for association at genetic regions previously associated with caries in primary and permanent dentition, including the beta-defensin anti-microbial proteins. We then integrated the meta-analysis results with gene expression data in a transcriptome-wide association study (TWAS). This approach identified four genes whose genetically predicted expression was associated with ECC (p-values < 3.09 x 10(-6); CDH17, TAS2R43, SMIM10L1, TAS2R14). Some of the strongest associations were with genes encoding members of the bitter taste receptor family (TAS2R); other members of this family have previously been associated with caries. Of note, we identified the receptor encoded by TAS2R14, which stimulates innate immunity and anti-microbial defense in response to molecules released by the cariogenic bacteria, Streptococcus mutans and Staphylococcus aureus. These findings provide insight into ECC genetic architecture, underscore the importance of host-microbial interaction in caries risk, and identify novel risk genes.
Details
- Title: Subtitle
- Association of Early Childhood Caries with Bitter Taste Receptors: A Meta-Analysis of Genome-Wide Association Studies and Transcriptome-Wide Association Study
- Creators
- Ekaterina Orlova - University of PittsburghTom Dudding - University of BristolJonathan M. Chernus - University of PittsburghRasha N. Alotaibi - King Saud UniversitySimon Haworth - University of BristolRichard J. Crout - West Virginia UniversityMyoung Keun Lee - University of PittsburghNandita Mukhopadhyay - University of PittsburghEleanor Feingold - University of PittsburghSteven M. Levy - University of IowaDaniel W. McNeil - West Virginia UniversityBetsy Foxman - Univ Michigan, Ctr Mol & Clin Epidemiol Infect Dis, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USARobert J. Weyant - University of PittsburghNicholas J. Timpson - University of BristolMary L. Marazita - University of PittsburghJohn R. Shaffer - University of Pittsburgh
- Resource Type
- Journal article
- Publication Details
- Genes, Vol.14(1), p.59
- DOI
- 10.3390/genes14010059
- PMID
- 36672800
- PMCID
- PMC9858612
- NLM abbreviation
- Genes (Basel)
- ISSN
- 2073-4425
- eISSN
- 2073-4425
- Publisher
- Mdpi
- Number of pages
- 17
- Grant note
- 23andMe UK Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 217065/Z/19/Z / Wellcome R01-DE014899; 1-U01-DE018903; X01-HG009878; R01-DE09551; P30-DE10126 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01-DE014899; 1-U01-DE018903; X01-HG009878 / U.S. National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 01/01/2023
- Academic Unit
- Preventive and Community Dentistry; Epidemiology
- Record Identifier
- 9984367589602771
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