使用全基因组生存分析确定与阿巴拉契亚地区龋齿发病率相关的潜在风险因素和基因变异
Potential risk factors and genetic variants associated with dental caries incidence in Appalachia using genome-wide survival analysis.
作者信息
Zou Tianyu, Neiswanger Katherine, Feingold Eleanor, Foxman Betsy, McNeil Daniel W, Marazita Mary L, Shaffer John R
机构信息
Department of Human Genetics, School of Public Health, University of Pittsburgh Pittsburgh, PA, USA.
Center for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh Pittsburgh, PA, USA.
出版信息
Int J Mol Epidemiol Genet. 2023 Aug 15;14(2):19-33. eCollection 2023.
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.
目的
本研究旨在通过生存分析确定与龋齿发病率相关的潜在风险因素和基因变异。
方法
阿巴拉契亚口腔健康研究中心招募并前瞻性跟踪孕妇及其子女。本研究纳入了909名从出生开始随访长达7年的儿童。每年进行口腔检查以评估龋齿情况，包括乳牙列首次发生龋齿的大致时间。使用Cox比例风险模型评估首次发生龋齿的时间与自我报告的风险因素以及使用全基因组基因分型阵列确定的490万个基因变异之间的关联。
结果
909名儿童中有196名（21.56%）在随访期间首次出现乳牙龋齿。在逐步Cox模型中，家庭收入、家庭水源和母亲的教育程度与首次发生龋齿的时间显著相关。首次发生龋齿时间的遗传度（即由基因解释的方差比例）为0.54。虽然在全基因组显著性水平（P < 5E-8）下没有特定的基因变异与之相关，但我们在提示性显著性水平（5E-8 < P < 1E-5）下确定了14个位点，其中一些位于在龋齿中具有合理生物学功能的基因内部或附近。
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病率的独立风险因素。我们提名了几个提示性位点以供进一步研究。
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