Potential risk factors and genetic variants associated with dental caries incidence in Appalachia using genome-wide survival analysis.

International journal of molecular epidemiology and genetics Pub Date : 2023-08-15 eCollection Date: 2023-01-01
Tianyu Zou, Katherine Neiswanger, Eleanor Feingold, Betsy Foxman, Daniel W McNeil, Mary L Marazita, John R Shaffer
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Abstract

Objective: The aim of this study was to identify the potential risk factors and genetic variants associated with dental caries incidence using survival analysis.

Methods: The Center for Oral Health Research in Appalachia recruited and prospectively followed pregnant women and their children. A total of 909 children followed from birth for up to 7 years were included in this study. Annual intra-oral examinations were performed to assess dental caries experience including the approximate time to first caries incidence in the primary dentition. Cox proportional hazards models were used to assess the associations of time to first caries incidence with self-reported risk factors and 4.9 million genetic variants ascertained using a genome-wide genotyping array.

Results: A total of 196 of 909 children (21.56%) had their first primary tooth caries event during follow-up. Household income, home water source, and mother's educational attainment were significantly associated with time to first caries incidence in the stepwise Cox model. The heritability (i.e., proportion of variance explained by genetics) of time to first caries was 0.54. Though no specific genetic variants were associated at the genome-wide significance level (P < 5E-8), we identified 14 loci at the suggestive significance level (5E-8 < P < 1E-5), some of which were located within or near genes with plausible biological functions in dental caries.

Conclusion: Our findings indicate that household income, home water source, and mother's educational attainment are independent risk factors for dental caries incidence. We nominate several suggestive loci for further investigation.

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应用全基因组生存分析分析阿巴拉契亚地区与龋齿发病率相关的潜在危险因素和遗传变异。
目的:本研究的目的是通过生存分析来确定与龋齿发病率相关的潜在危险因素和遗传变异。方法:阿巴拉契亚口腔健康研究中心招募孕妇及其子女进行前瞻性随访。本研究共纳入909名儿童,从出生起随访长达7年。每年进行一次口腔内检查,以评估龋齿经历,包括乳牙列中第一次龋齿发生的大致时间。Cox比例风险模型用于评估首次龋齿发病率与自我报告的风险因素和使用全基因组基因分型阵列确定的490万种遗传变异的相关性。结果:909名儿童中,共有196名(21.56%)在随访期间发生了第一次乳牙龋齿事件。在逐步Cox模型中,家庭收入、家庭水源和母亲的教育程度与第一次龋齿发生率显著相关。第一次龋齿发生时间的遗传力(即遗传学解释的方差比例)为0.54。尽管在全基因组显著性水平上没有特定的遗传变异相关(P<5E-8),但我们在提示性显著性水平(5E-8<P<1E-5)上鉴定了14个基因座,其中一些位于在龋齿中具有合理生物学功能的基因内或附近。结论:我们的研究结果表明,家庭收入、家庭水源和母亲的教育程度是龋齿发生的独立危险因素。我们提名了几个提示性位点进行进一步研究。
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