{"doi":"10.3390/genes14010059","title":"Association of Early Childhood Caries with Bitter Taste Receptors: A Meta-Analysis of Genome-Wide Association Studies and Transcriptome-Wide Association Study","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 ~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 β-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 × 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.","journal":"Genes","year":2022,"id":257105,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8899,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":261925,"name":"Tom Dudding","orcid":"0000-0003-3756-040X","position":1,"is_corresponding":false},{"id":669193,"name":"Jonathan M. Chernus","orcid":"0000-0001-6555-1143","position":2,"is_corresponding":false},{"id":669192,"name":"Rasha N. Alotaibi","orcid":"0000-0001-6455-9522","position":3,"is_corresponding":false},{"id":560480,"name":"Simon Haworth","orcid":"0000-0001-7793-7326","position":4,"is_corresponding":false},{"id":598678,"name":"Richard J. Crout","orcid":"0000-0002-7695-5685","position":5,"is_corresponding":false},{"id":557775,"name":"Myoung Keun Lee","orcid":"0000-0003-1508-9661","position":6,"is_corresponding":false},{"id":284224,"name":"Nandita Mukhopadhyay","orcid":"0000-0001-7117-9536","position":7,"is_corresponding":false},{"id":284228,"name":"Eleanor Feingold","orcid":"0000-0003-2898-6484","position":8,"is_corresponding":false},{"id":399802,"name":"Steven M. Levy","orcid":"0000-0001-9150-4199","position":9,"is_corresponding":false},{"id":453654,"name":"Daniel W. McNeil","orcid":"0000-0002-0766-8455","position":10,"is_corresponding":false},{"id":317975,"name":"Betsy Foxman","orcid":"0000-0001-6682-238X","position":11,"is_corresponding":false},{"id":339725,"name":"Robert J. Weyant","orcid":"0000-0002-5252-9120","position":12,"is_corresponding":false},{"id":42602,"name":"Nicholas J. Timpson","orcid":"0000-0002-7141-9189","position":13,"is_corresponding":false},{"id":284230,"name":"Mary L. Marazita","orcid":"0000-0002-2648-2832","position":14,"is_corresponding":false},{"id":378328,"name":"John R. Shaffer","orcid":"0000-0003-1897-1131","position":15,"is_corresponding":false},{"id":907019,"name":"Ekaterina Orlova","orcid":"0000-0002-7129-5796","position":0,"is_corresponding":true}],"reference_count":148,"raw_metadata":null,"created_at":"2026-07-19T00:25:30.183987Z","pmid":"36672800","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}