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• W4318159672 abstract "Abstract Apical periodontitis (AP) is a common consequence of root canal infection leading to periapical bone resorption. Microbial and host genetic factors, and their interactions, have been shown to play a role in AP development and progression. Variations in a few genes have been reported in association with AP, however, the lack of genome-wide studies has hindered progress in understanding the mechanisms involved in AP. Here, we report the first genome-wide association study of AP in a well-characterized population. Male and female adults (n=932) presenting with deep caries with AP (cases) or without AP (controls) were included. Genotyping was performed using the Illumina Expanded Multi-Ethnic Genotyping Array. Single-variant association testing was performed adjusting for sex and five principal components. Subphenotype association testing, analyses of genetically regulated gene expression, polygenic risk score and phenome-wide association (PheWAS) analyses were also performed. Eight loci reached near-genome-wide significant association with AP (p < 5 x 10-6); gene-focused analyses replicated three previously reported associations (p < 8.9 x 10-5). Sex-specific and subphenotype analyses revealed additional significant associations with variants genome-wide. Functionally oriented gene-based analyses revealed eight genes significantly associated with AP (p < 5 x 10-5), and PheWAS analysis revealed 33 phecodes associated with AP risk score (p < 3.08 x 10-5). This study identified novel genes/loci contributing to AP and revealed specific contributions to AP risk in males and females. Importantly, we identified additional systemic conditions significantly associated with AP risk. Our findings provide strong evidence for host-mediated effects on AP susceptibility." @default.
• W4318159672 created "2023-01-27" @default.
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• W4318159672 date "2023-01-26" @default.
• W4318159672 modified "2023-09-27" @default.
• W4318159672 title "Genome-wide association study identifies novel risk loci for apical periodontitis" @default.
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• W4318159672 doi "https://doi.org/10.21203/rs.3.rs-2515434/v1" @default.
• W4318159672 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36747740" @default.
• W4318159672 hasPublicationYear "2023" @default.
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