Genome-wide Association Study Identifies Novel Risk Loci for Apical Periodontitis.

Autor:	Petty LE; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee., Silva R; Department of Endodontics, University of Pittsburgh School of Dental Medicine, Pittsburgh, Pennsylvania., de Souza LC; Department of Endodontics, UTHealth School of Dentistry at Houston, Houston, Texas., Vieira AR; Department of Oral and Craniofacial Sciences, University of Pittsburgh School of Dental Medicine, Pittsburgh, Pennsylvania., Shaw DM; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee., Below JE; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee., Letra A; Department of Endodontics, University of Pittsburgh School of Dental Medicine, Pittsburgh, Pennsylvania; Department of Endodontics, UTHealth School of Dentistry at Houston, Houston, Texas; Department of Diagnostic and Biomedical Sciences, UTHealth School of Dentistry at Houston, Houston, Texas; Center for Craniofacial Research, UTHealth School of Dentistry at Houston, Houston, Texas. Electronic address: AriadneLetra@pitt.edu.
Jazyk:	angličtina
Zdroj:	Journal of endodontics [J Endod] 2023 Oct; Vol. 49 (10), pp. 1276-1288. Date of Electronic Publication: 2023 Jul 25.
DOI:	10.1016/j.joen.2023.07.018
Abstrakt:	Introduction: 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 molecular mechanisms involved. Here, we report the first genome-wide association study of AP in a large and well-characterized population. Methods: Male and female adults (n = 932) presenting with deep caries and AP (cases), or deep caries without AP (controls) were included. Genotyping was performed using the Illumina Expanded Multi-Ethnic Genotyping Array (MEGA). Single-variant association testing was performed adjusting for sex and 5 principal components. Subphenotype association testing, analyses of genetically regulated gene expression, polygenic risk score, and phenome-wide association (PheWAS) analyses were also conducted. Results: Eight loci reached near genome-wide significant association with AP (P < 5 × 10 -6 ); gene-focused analyses replicated 3 previously reported associations (P < 8.9 × 10 -5 ). Sex-specific and subphenotype-specific analyses revealed additional significant associations with variants genome-wide. Functionally oriented gene-based analyses revealed 8 genes significantly associated with AP (P < 5 × 10 -5 ), and PheWAS analysis revealed 33 phecodes associated with AP risk score (P < 3.08 × 10 -5 ). Conclusions: This study identified novel genes/loci contributing to AP and specific contributions to AP risk in men and women. Importantly, we identified additional systemic conditions significantly associated with AP risk. Our findings provide strong evidence for host-mediated effects on AP susceptibility. (Copyright © 2023 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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